Mangifera indica (Mango): A Promising Medicinal Plant for Breast Cancer Therapy and Understanding Its Potential Mechanisms of Action

References

• SiegelRL, MillerKD, JemalA. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi:10.3322/caac.2133226742998
   PubMed Web of Science ®Google Scholar
• SungH, FerlayJ, SiegelRL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.2166033538338
   PubMed Web of Science ®Google Scholar
• KenneckeH, YerushalmiR, WoodsR, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–3277. doi:10.1200/JCO.2009.25.982020498394
   PubMed Web of Science ®Google Scholar
• SunYS, ZhaoZ, YangZN, et al. Risk factors and preventions of breast cancer. Int J Biol Sci. 2017;13(11):1387–1397. doi:10.7150/ijbs.2163529209143
   PubMed Web of Science ®Google Scholar
• Abu-HelalahM, AzabB, MubaidinR, et al. BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan. Sci Rep. 2020;10(1):17573. doi:10.1038/s41598-020-74250-233067490
   PubMed Web of Science ®Google Scholar
• LarsenMJ, ThomassenM, GerdesAM, KruseTA. Hereditary breast cancer: clinical, pathological and molecular characteristics. Breast Cancer (Auckl). 2014;8:145–155.25368521
   PubMedGoogle Scholar
• KorenS, Bentires-AljM. Breast tumor heterogeneity: source of fitness, hurdle for therapy. Mol Cell. 2015;60(4):537–546. doi:10.1016/j.molcel.2015.10.03126590713
   PubMed Web of Science ®Google Scholar
• NielsenTO, HsuFD, JensenK, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367–5374. doi:10.1158/1078-0432.CCR-04-022015328174
   PubMed Web of Science ®Google Scholar
• WaksAG, WinerEP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300. doi:10.1001/jama.2018.1932330667505
   PubMed Web of Science ®Google Scholar
• FragomeniSM, SciallisA, JerussJS. Molecular subtypes and local-regional control of breast cancer. Surg Oncol Clin N Am. 2018;27(1):95–120. doi:10.1016/j.soc.2017.08.00529132568
   PubMed Web of Science ®Google Scholar
• LeiJT, AnuragM, HaricharanS, GouX, EllisMJ. Endocrine therapy resistance: new insights. Breast. 2019;48(Suppl 1):S26–S30. doi:10.1016/S0960-9776(19)31118-X31839155
   PubMed Web of Science ®Google Scholar
• AysolaK, DesaiA, WelchC, et al. Triple negative breast cancer – an overview. Hereditary Genet. 2013;Suppl 2:1.
   Google Scholar
• MukherjeeAK, BasuS, SarkarN, GhoshAC. Advances in cancer therapy with plant based natural products. Curr Med Chem. 2001;8(12):1467–1486. doi:10.2174/092986701337209411562277
   PubMed Web of Science ®Google Scholar
• MondalS, BandyopadhyayS, GhoshMK, MukhopadhyayS, RoyS, MandalC. Natural products: promising resources for cancer drug discovery. Anticancer Agents Med Chem. 2012;12(1):49–75. doi:10.2174/18715201279876469721707502
   PubMed Web of Science ®Google Scholar
• BonofiglioD, GiordanoC, De AmicisF, LanzinoM, AndòS. Natural products as promising antitumoral agents in breast cancer: mechanisms of action and molecular targets. Mini Rev Med Chem. 2016;16(8):596–604. doi:10.2174/138955751566615070911095926156544
   PubMed Web of Science ®Google Scholar
• KhalidF, NawazH, HanifMA, RehmanR, Al-SadiAM. Mango. Medicinal Plants of South Asia: Novel Sources for Drug Discovery. Amsterdam, Oxford, Cambridge MA: Elsevier; 2020:495–508.
   Google Scholar
• MasiboM, HeQ. Major mango polyphenols and their potential significance to human health. Compr Rev Food Sci Food Saf. 2008;7(4):309–319. doi:10.1111/j.1541-4337.2008.00047.x33467788
   PubMed Web of Science ®Google Scholar
• DereseS, GuantaiEM, SouaibouY, KueteV. Mangifera indica L. (Anacardiaceae). Medicinal Spices and Vegetables from Africa. London, San Diego, Cambridge MA, Oxford: Elsevier; 2017:451–483.
   Google Scholar
• ShahKA, PatelMB, PatelRJ, ParmarPK. Mangifera indica (Mango). Pharmacogn Rev. 2010;4(7):42–48. doi:10.4103/0973-7847.6532522228940
   PubMedGoogle Scholar
• El-GiedAAA, JosephMR, MahmoudIM, AbdelkareemAM, Al HakamiAM, HamidME. Antimicrobial activities of seed extracts of mango (Mangifera indica L.). Adv Microbiol. 2012;2(4):571–576. doi:10.4236/aim.2012.24074
   Google Scholar
• KabukiT, NakajimaH, AraiM, UedaS, KuwabaraY, DosakoS. Characterization of novel antimicrobial compounds from mango (Mangifera indica L.) kernel seeds. Food Chem. 2000;71(1):61–66. doi:10.1016/S0308-8146(00)00126-6
   Web of Science ®Google Scholar
• MakareN, BodhankarS, RangariV. Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice. J Ethnopharmacol. 2001;78(2–3):133–137. doi:10.1016/S0378-8741(01)00326-911694357
   PubMed Web of Science ®Google Scholar
• MartinezG, DelgadoR, PérezG, GarridoG, Núñez-SellésA, LeónOS. Evaluation of the in vitro antioxidant activity of Mangifera indica L. extract (Vimang). Phytother Res. 2000;14(6):424–427. doi:10.1002/1099-1573(200009)14:6<424::AID-PTR643>3.0.CO;2-810960895
   PubMed Web of Science ®Google Scholar
• BanerjeeN, KimH, KrenekK, TalcottST, Mertens-TalcottSU. Mango polyphenolics suppressed tumor growth in breast cancer xenografts in mice: role of the PI3K/AKT pathway and associated microRNAs. Nutr Res. 2015;35(8):744–751. doi:10.1016/j.nutres.2015.06.00226194618
   PubMed Web of Science ®Google Scholar
• García-SolísP, YahiaEM, Morales-TlalpanV, Díaz-MuñozM. Screening of antiproliferative effect of aqueous extracts of plant foods consumed in Mexico on the breast cancer cell line MCF-7. Int J Food Sci Nutr. 2009;60(Suppl 6):32–46. doi:10.1080/09637480802312922
   Web of Science ®Google Scholar
• WilkinsonAS, FlanaganBM, PiersonJT, et al. Bioactivity of mango flesh and peel extracts on peroxisome proliferator‐activated receptor γ[PPARγ] activation and MCF‐7 cell proliferation: fraction and fruit variability. J Food Sci. 2011;76(1):H11–H18. doi:10.1111/j.1750-3841.2010.01899.x21535682
   PubMed Web of Science ®Google Scholar
• Fernández-PonceMT, López-BiedmaA, Sánchez-QuesadaC, et al. Selective antitumoural action of pressurized mango leaf extracts against minimally and highly invasive breast cancer. Food Funct. 2017;8(10):3610–3620. doi:10.1039/C7FO00877E28891568
   PubMed Web of Science ®Google Scholar
• López-RíosL, WiebeJC, Vega-MoralesT, GerickeN. Central nervous system activities of extract Mangifera indica L. J Ethnopharmacol. 2020;260:112996. doi:10.1016/j.jep.2020.11299632473365
   PubMed Web of Science ®Google Scholar
• VenancioVP, KimH, SirvenMA, et al. Polyphenol-rich mango (Mangifera indica L.) ameliorate functional constipation symptoms in humans beyond equivalent amount of fiber. Mol Nutr Food Res. 2018;62(12):e1701034. doi:10.1002/mnfr.20170103429733520
   PubMed Web of Science ®Google Scholar
• Anaya-LoyolaMA, García-MarínG, García-GutiérrezDG, et al. A mango (Mangifera indica L.) juice by-product reduces gastrointestinal and upper respiratory tract infection symptoms in children. Food Res Int. 2020;136:109492. doi:10.1016/j.foodres.2020.10949232846573
   PubMed Web of Science ®Google Scholar
• López MantecónAM, GarridoG, Delgado-HernándezR, Garrido-SuárezBB. Combination of Mangifera indica L. extract supplementation plus methotrexate in rheumatoid arthritis patients: a pilot study. Phytother Res. 2014;28(8):1163–1172. doi:10.1002/ptr.510824344049
   PubMed Web of Science ®Google Scholar
• RodeiroI, DonatoMT, JiménezN, GarridoG, DelgadoR, Gómez-LechónMJ. Effects of Mangifera indica L. aqueous extract (Vimang) on primary culture of rat hepatocytes. Food Chem Toxicol. 2007;45(12):2506–2512. doi:10.1016/j.fct.2007.05.02717651882
   PubMed Web of Science ®Google Scholar
• Núñez SellésAJ, Vélez CastroHT, Agüero-AgüeroJ, et al. Isolation and quantitative analysis of phenolic antioxidants, free sugars, and polyols from mango (Mangifera indica L.) stem bark aqueous decoction used in Cuba as a nutritional supplement. J Agric Food Chem. 2002;50(4):762–766. doi:10.1021/jf011064b11829642
   PubMed Web of Science ®Google Scholar
• García-RiveraD, DelgadoR, BougarneN, HaegemanG, BergheWV. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells. Cancer Lett. 2011;305(1):21–31. doi:10.1016/j.canlet.2011.02.01121420233
   PubMed Web of Science ®Google Scholar
• Pardo-AndreuGL, DortaDJ, DelgadoR, et al. Vimang (Mangifera indica L. extract) induces permeability transition in isolated mitochondria, closely reproducing the effect of mangiferin, Vimang’s main component. Chem Biol Interact. 2006;159(2):141–148. doi:10.1016/j.cbi.2005.10.10916352298
   PubMed Web of Science ®Google Scholar
• GarridoG, GonzálezD, DelporteC, et al. Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang). Phytother Res. 2001;15(1):18–21. doi:10.1002/1099-1573(200102)15:1<18::AID-PTR676>3.0.CO;2-R11180516
   PubMed Web of Science ®Google Scholar
• GarridoG, Blanco-MolinaM, SanchoR, MachoA, DelgadoR, MuñozE. An aqueous stem bark extract of Mangifera indica (Vimang) inhibits T cell proliferation and TNF-induced activation of nuclear transcription factor NF-kappaB. Phytother Res. 2005;19(3):211–215. doi:10.1002/ptr.165615934029
   PubMed Web of Science ®Google Scholar
• TamayoD, MariE, GonzalezS, et al. Vimang as natural antioxidant supplementation in patients with malignant tumors. Minerva Med. 2001;92(Suppl 1–3):95–97.
   Google Scholar
• AbdullahAH, MohammedAS, AbdullahR, MirghaniMES, Al-QubaisiM. Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract. BMC Complement Altern Med. 2014;14(1):199. doi:10.1186/1472-6882-14-19924962691
   PubMed Web of Science ®Google Scholar
• BlackHS, Mathews-RothMM. Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Photochem Photobiol. 1991;53(5):707–716. doi:10.1111/j.1751-1097.1991.tb08501.x1881965
   PubMed Web of Science ®Google Scholar
• SaitoM, SakagamiH, FujisawaS. Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Anticancer Res. 2003;23(6C):4693–4701.14981915
   PubMed Web of Science ®Google Scholar
• KurodaK, AkaoM. Antitumor and anti-intoxication activities of fumaric acid in cultured cells. Gan. 1981;72(5):777–782.7327376
   PubMedGoogle Scholar
• KurodaK, TeraoK, AkaoM. Inhibitory effect of fumaric acid on hepatocarcinogenesis by thioacetamide in rats. J Natl Cancer Inst. 1987;79(5):1047–1051.3479633
   PubMed Web of Science ®Google Scholar
• OkokonJE, DarA, ChoudharyMI. Immunomodulatory, cytotoxic and antileishmanial activity of phytoconstituents of Croton zambesicus. Phytopharmacol. 2013;4(1):31–40.
   Google Scholar
• SmiljkovicM, StanisavljevicD, StojkovicD, et al. Apigenin-7-O-glucoside versus apigenin: insight into the modes of anticandidal and cytotoxic actions. EXCLI J. 2017;16:795–807.28827996
   PubMed Web of Science ®Google Scholar
• SrivastavaJ, GuptaS. Anti-proliferative and apoptotic effects of chamomile extract in various human cancer cells. J Agric Food Chem. 2007;55(23):9470–9478. doi:10.1021/jf071953k17939735
   PubMed Web of Science ®Google Scholar
• PosnerGH, PloypradithP, HapangamaW, et al. Trioxane dimers have potent antimalarial, antiproliferative and antitumor activities in vitro. Bioorg Med Chem. 1997;5(7):1257–1265. doi:10.1016/S0968-0896(97)00079-59377085
   PubMed Web of Science ®Google Scholar
• ShacterE, WeitzmanSA. Chronic inflammation and cancer. Oncology. 2002;16(2):217–226, 229.11866137
   PubMed Web of Science ®Google Scholar
• BarretoJC, TrevisanMTS, HullWE, et al. Characterization and quantitation of polyphenolic compounds in bark, kernel, leaves, and peel of mango (Mangifera indica L.). J Agric Food Chem. 2008;56(14):5599–5610. doi:10.1021/jf800738r18558692
   PubMed Web of Science ®Google Scholar
• GanogpichayagraiA, PalanuvejC, RuangrungsiN. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves. J Adv Pharm Technol Res. 2017;8(1):19–24. doi:10.4103/2231-4040.19737128217550
   PubMed Web of Science ®Google Scholar
• ShabanNZ, HegazyWA, Abdel-RahmanSM, AwedOM, KhalilSA. Potential effect of Olea europaea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: comparative study. Cell Mol Biol (Noisy-Le-Grand). 2016;62(9):11–19.
   PubMed Web of Science ®Google Scholar
• HoangVLT, PiersonJT, CurryMC, et al. Polyphenolic contents and the effects of methanol extracts from mango varieties on breast cancer cells. Food Sci Biotechnol. 2015;24(1):265–271. doi:10.1007/s10068-015-0035-x
   Web of Science ®Google Scholar
• TaingMW, PiersonJT, ShawPN, et al. Mango fruit extracts differentially affect proliferation and intracellular calcium signalling in MCF-7 human breast cancer cells. J Chem. 2015;2015:1–10. doi:10.1155/2015/613268
   Web of Science ®Google Scholar
• PiersonJT, MonteithGR, Roberts-ThomsonSJ, DietzgenRG, GidleyMJ, ShawPN. Phytochemical extraction, characterisation and comparative distribution across four mango (Mangifera indica L.) fruit varieties. Food Chem. 2014;149:253–263. doi:10.1016/j.foodchem.2013.10.10824295704
   PubMed Web of Science ®Google Scholar
• NorattoGD, BertoldiMC, KrenekK, TalcottST, StringhetaPC, Mertens-TalcottSU. Anticarcinogenic effects of polyphenolics from mango (Mangifera indica) varieties. J Agric Food Chem. 2010;58(7):4104–4112. doi:10.1021/jf903161g20205391
   PubMed Web of Science ®Google Scholar
• NemecMJ, KimH, MarcianteAB, BarnesRC, TalcottST, Mertens-TalcottSU. Pyrogallol, an absorbable microbial gallotannins-metabolite and mango polyphenols (Mangifera Indica L.) suppress breast cancer ductal carcinoma in situ proliferation in vitro. Food Funct. 2016;7(9):3825–3833. doi:10.1039/C6FO00636A27491891
   PubMed Web of Science ®Google Scholar
• NemecMJ, KimH, MarcianteAB, et al. Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice. J Nutr Biochem. 2017;41:12–19. doi:10.1016/j.jnutbio.2016.11.00527951515
   PubMed Web of Science ®Google Scholar
• BenardO, ChiY. Medicinal properties of mangiferin, structural features, derivative synthesis. Pharmacokinetics Biol Activities Mini Rev Med Chem. 2015;15(7):582–594. doi:10.2174/1389557515666150401111410
   Web of Science ®Google Scholar
• BiswasT, SenA, RoyR, MajiS, MajiHS. Isolation of mangiferin from flowering buds of Mangifera indica L and its evaluation of in vitro antibacterial activity. J Pharm Anal. 2015;4(3):49–56.
   Google Scholar
• DarA, FaiziS, NaqviS, et al. Analgesic and antioxidant activity of mangiferin and its derivatives: the structure activity relationship. Biol Pharm Bull. 2005;28(4):596–600. doi:10.1248/bpb.28.59615802793
   PubMed Web of Science ®Google Scholar
• GongX, ZhangL, JiangR, YeM, YinX, WanJ. Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1. J Nutr Biochem. 2013;24(6):1173–1181. doi:10.1016/j.jnutbio.2012.09.00323266284
   PubMed Web of Science ®Google Scholar
• MiuraT, IchikiH, HashimotoI, et al. Antidiabetic activity of a xanthone compound, mangiferin. Phytomedicine. 2001;8(2):85–87. doi:10.1078/0944-7113-0000911315760
   PubMed Web of Science ®Google Scholar
• Núñez SellesAJ, DagliaM, RastrelliL. The potential role of mangiferin in cancer treatment through its immunomodulatory, anti-angiogenic, apoptopic, and gene regulatory effects. Biofactors. 2016;42(5):475–491. doi:10.1002/biof.129927219221
   PubMed Web of Science ®Google Scholar
• RajendranP, JayakumarT, NishigakiI, et al. Immunomodulatory effect of mangiferin in experimental animals with benzo(a)pyrene-induced lung carcinogenesis. Int J Biomed Sci. 2013;9(2):68–74.23847456
   PubMedGoogle Scholar
• ImranM, ArshadMS, ButtMS, KwonJH, ArshadMU, SultanMT. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis. 2017;16(1):84. doi:10.1186/s12944-017-0449-y28464819
   PubMed Web of Science ®Google Scholar
• LiH, HuangJ, YangB, et al. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway. Toxicol Appl Pharmacol. 2013;272(1):180–190. doi:10.1016/j.taap.2013.05.01123707762
   PubMed Web of Science ®Google Scholar
• DengQ, TianYX, LiangJ. Mangiferin inhibits cell migration and invasion through Rac1/WAVE2 signalling in breast cancer. Cytotechnology. 2018;70(2):593–601. doi:10.1007/s10616-017-0140-129455393
   PubMed Web of Science ®Google Scholar
• CuccioloniM, BonfiliL, MozzicafreddoM, et al. Mangiferin blocks proliferation and induces apoptosis of breast cancer cells via suppression of mevalonate pathway and by proteasome inhibition. Food Funct. 2016;7(10):4299–4309. doi:10.1039/C6FO01037G27722367
   PubMed Web of Science ®Google Scholar
• ThornCF, OshiroC, MarshS, et al. Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2011;21(7):440–446. doi:10.1097/FPC.0b013e32833ffb5621048526
   PubMed Web of Science ®Google Scholar
• Al-MalkyHS, Al HarthiSE, OsmanAMM. Major obstacles to doxorubicin therapy: cardiotoxicity and drug resistance. J Oncol Pharm Pract. 2020;26(2):434–444. doi:10.1177/107815521987793131594518
   PubMed Web of Science ®Google Scholar
• MechetnerE, KyshtoobayevaA, ZonisS, et al. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res. 1998;4(2):389–398.9516927
   PubMed Web of Science ®Google Scholar
• SargentJM, WilliamsonCJ, MaliepaardM, ElgieAW, ScheperRJ, TaylorCG. Breast cancer resistance protein expression and resistance to daunorubicin in blast cells from patients with acute myeloid leukaemia. Br J Haematol. 2001;115(2):257–262. doi:10.1046/j.1365-2141.2001.03122.x11703319
   PubMed Web of Science ®Google Scholar
• ZhangYK, WangYJ, GuptaP, ChenZS. Multidrug resistance proteins (MRPs) and cancer therapy. AAPS J. 2015;17(4):802–812. doi:10.1208/s12248-015-9757-125840885
   PubMed Web of Science ®Google Scholar
• LouisaM, SoediroTM, SuyatnaFD. In vitro modulation of P-glycoprotein, MRP-1 and BCRP expression by mangiferin in doxorubicin-treated MCF-7 cells. Asian Pac J Cancer Prev. 2014;15(4):1639–1642. doi:10.7314/APJCP.2014.15.4.163924641381
   PubMedGoogle Scholar
• WilkinsonAS, TaingMW, PiersonJT, et al. Estrogen modulation properties of mangiferin and quercetin and the mangiferin metabolite norathyriol. Food Funct. 2015;6(6):1847–1854. doi:10.1039/C5FO00133A25940566
   PubMed Web of Science ®Google Scholar
• WangF, YanJ, NiuY, et al. Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase. Pharm Biol. 2014;52(1):68–73. doi:10.3109/13880209.2013.81469124033319
   PubMed Web of Science ®Google Scholar
• HanB, YangB, YangX, et al. Host-guest inclusion system of norathyriol with β-cyclodextrin and its derivatives: preparation, characterization, and anticancer activity. J Biosci Bioeng. 2014;117(6):775–779. doi:10.1016/j.jbiosc.2013.12.00124508024
   PubMed Web of Science ®Google Scholar
• SanugulK, AkaoT, LiY, KakiuchiN, NakamuraN, HattoriM. Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond. Biol Pharm Bull. 2005;28(9):1672–1678. doi:10.1248/bpb.28.167216141538
   PubMed Web of Science ®Google Scholar
• ShiZL, LiuYD, YuanYY, et al. In vitro and in vivo effects of norathyriol and mangiferin on α-glucosidase. Biochem Res Int. 2017;2017:1206015. doi:10.1155/2017/120601528168055
   PubMed Web of Science ®Google Scholar
• WangJP, HoTF, LinCN, TengCM. Effect of norathyriol, isolated from Tripterospermum lanceolatum, on A23187-induced pleurisy and analgesia in mice. Naunyn Schmiedebergs Arch Pharmacol. 1994;350(1):90–95. doi:10.1007/BF001800167935860
   PubMed Web of Science ®Google Scholar
• LiJ, MalakhovaM, MottamalM, et al. Norathyriol suppresses solar UV-induced skin cancer by targeting ERKs. Cancer Res. 2012;72(1):260–270. doi:10.1158/0008-5472.CAN-11-259622084399
   PubMed Web of Science ®Google Scholar
• TengCM, KoFN, WangJP, et al. Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs. J Pharm Pharmacol. 1991;43(9):667–669. doi:10.1111/j.2042-7158.1991.tb03561.x1685529
   PubMed Web of Science ®Google Scholar
• KoFN, LinCN, LiouSS, HuangTF, TengCM. Vasorelaxation of rat thoracic aorta caused by norathyriol isolated from Gentianaceae. Eur J Pharmacol. 1991;192(1):133–139. doi:10.1016/0014-2999(91)90079-61645671
   PubMed Web of Science ®Google Scholar
• BarnesRC, KimH, FangC, et al. Body mass index as a determinant of systemic exposure to gallotannin metabolites during 6‐week consumption of mango (Mangifera indica L.) and modulation of intestinal microbiota in lean and obese individuals. Mol Nutr Food Res. 2019;63(2):e1800512. doi:10.1002/mnfr.20180051230427574
   PubMed Web of Science ®Google Scholar
• FarràsM, Martinez-GiliL, PortuneK, et al. Modulation of the gut microbiota by olive oil phenolic compounds: implications for lipid metabolism, immune system, and obesity. Nutrients. 2020;12(8):2200. doi:10.3390/nu12082200
   PubMed Web of Science ®Google Scholar
• GaliHU, PerchelletEM, GaoXM, BottariV, PerchelletJP. Antitumor-promoting effects of gallotannins extracted from various sources in mouse skin in vivo. Anticancer Res. 1993;13(4):915–922.7688939
   PubMed Web of Science ®Google Scholar
• HuhJE, LeeEO, KimMS, et al. Penta-O-galloyl-beta-D-glucose suppresses tumor growth via inhibition of angiogenesis and stimulation of apoptosis: roles of cyclooxygenase-2 and mitogen-activated protein kinase pathways. Carcinogenesis. 2005;26(8):1436–1445. doi:10.1093/carcin/bgi09715845650
   PubMed Web of Science ®Google Scholar
• MizushinaY, ZhangJ, PuglieseA, KimSH, LüJ. Anti-cancer gallotannin penta-O-galloyl-beta-D-glucose is a nanomolar inhibitor of select mammalian DNA polymerases. Biochem Pharmacol. 2010;80(8):1125–1132. doi:10.1016/j.bcp.2010.06.03120599777
   PubMed Web of Science ®Google Scholar
• MohanCG, ViswanathaGL, SavinayG, RajendraCE, HalemaniPD. 1,2,3,4,6 Penta-O-galloyl-β-d-glucose, a bioactivity guided isolated compound from Mangifera indica inhibits 11β-HSD-1 and ameliorates high fat diet-induced diabetes in C57BL/6 mice. Phytomedicine. 2013;20(5):417–426. doi:10.1016/j.phymed.2012.12.02023353053
   PubMed Web of Science ®Google Scholar
• ErdèlyiK, KissA, BakondiE, et al. Gallotannin inhibits the expression of chemokines and inflammatory cytokines in A549 cells. Mol Pharmacol. 2005;68(3):895–904. doi:10.1124/mol.105.01251815976037
   PubMed Web of Science ®Google Scholar
• EngelsC, KnödlerM, ZhaoYY, CarleR, GänzleMG, SchieberA. Antimicrobial activity of gallotannins isolated from mango (Mangifera indica L.) kernels. J Agric Food Chem. 2009;57(17):7712–7718. doi:10.1021/jf901621m19655802
   PubMed Web of Science ®Google Scholar
• CaiY, LuoQ, SunM, CorkeH. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci. 2004;74(17):2157–2184. doi:10.1016/j.lfs.2003.09.04714969719
   PubMed Web of Science ®Google Scholar
• LimKJA, CabajarAA, LobarbioCFY, TaboadaEB, LacksDJ. Extraction of bioactive compounds from mango (Mangifera indica L. var. Carabao) seed kernel with ethanol-water binary solvent systems. J Food Sci Technol. 2019;56(5):2536–2544. doi:10.1007/s13197-019-03732-731168135
   PubMed Web of Science ®Google Scholar
• HuaKT, WayTD, LinJK. Pentagalloylglucose inhibits estrogen receptor alpha by lysosome-dependent depletion and modulates ErbB/PI3K/Akt pathway in human breast cancer MCF-7 cells. Mol Carcinog. 2006;45(8):551–560. doi:10.1002/mc.2022616637063
   PubMed Web of Science ®Google Scholar
• ChenWJ, ChangCY, LinJK. Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip). Biochem Pharmacol. 2003;65(11):1777–1785. doi:10.1016/S0006-2952(03)00156-412781329
   PubMed Web of Science ®Google Scholar
• KahkeshaniN, FarzaeiF, FotouhiM, et al. Pharmacological effects of gallic acid in health and diseases: a mechanistic review. Iran J Basic Med Sci. 2019;22(3):225–237.31156781
   PubMed Web of Science ®Google Scholar
• KimSH, JunCD, SukK, et al. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol Sci. 2006;91(1):123–131. doi:10.1093/toxsci/kfj06316322071
   PubMed Web of Science ®Google Scholar
• KroesBH. Anti-inflammatory activity of gallic acid. Planta Med. 1992;58(6):499–504. doi:10.1055/s-2006-9615351336604
   PubMed Web of Science ®Google Scholar
• SorrentinoE, SucciM, TipaldiL, et al. Antimicrobial activity of gallic acid against food-related Pseudomonas strains and its use as biocontrol tool to improve the shelf life of fresh black truffles. Int J Food Microbiol. 2018;266:183–189. doi:10.1016/j.ijfoodmicro.2017.11.02629227905
   PubMed Web of Science ®Google Scholar
• GichnerT, PospísilF, VelemínskýJ, VolkeováV, VolkeJ. Two types of antimutagenic effects of gallic and tannic acids towards N-nitroso-compounds-induced mutagenicity in the Ames Salmonella assay. Folia Microbiol (Praha). 1987;32(1):55–62. doi:10.1007/BF028772593546027
   PubMed Web of Science ®Google Scholar
• Velderrain-RodríguezGR, Torres-MorenoH, Villegas-OchoaMA, et al. Gallic acid content and an antioxidant mechanism are responsible for the antiproliferative activity of ‘Ataulfo’ mango peel on LS180 cells. Molecules. 2018;23(3):695. doi:10.3390/molecules23030695
   PubMed Web of Science ®Google Scholar
• ZhaoB, HuM. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells. Oncol Lett. 2013;6(6):1749–1755. doi:10.3892/ol.2013.163224843386
   PubMed Web of Science ®Google Scholar
• SubramanianAP, JaganathanSK, MandalM, SupriyantoE, MuhamadII. Gallic acid induced apoptotic events in HCT-15 colon cancer cells. World J Gastroenterol. 2016;22(15):3952–3961. doi:10.3748/wjg.v22.i15.395227099438
   PubMed Web of Science ®Google Scholar
• FariedA, KurniaD, FariedLS, et al. Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. Int J Oncol. 2007;30(3):605–613.17273761
   PubMed Web of Science ®Google Scholar
• TsaiCL, ChiuYM, HoTY, et al. Gallic acid induces apoptosis in human gastric adenocarcinoma cells. Anticancer Res. 2018;38(4):2057–2067.29599323
   PubMed Web of Science ®Google Scholar
• LuY, JiangF, JiangH, et al. Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells. Eur J Pharmacol. 2010;641(2–3):102–107. doi:10.1016/j.ejphar.2010.05.04320553913
   PubMed Web of Science ®Google Scholar
• GuR, ZhangM, MengH, XuD, XieY. Gallic acid targets acute myeloid leukemia via Akt/mTOR-dependent mitochondrial respiration inhibition. Biomed Pharmacother. 2018;105:491–497. doi:10.1016/j.biopha.2018.05.15829883944
   PubMed Web of Science ®Google Scholar
• SunG, ZhangS, XieY, ZhangZ, ZhaoW. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. Oncol Lett. 2016;11(1):150–158. doi:10.3892/ol.2015.384526870182
   PubMed Web of Science ®Google Scholar
• ZhangT, MaL, WuP, et al. Gallic acid has anticancer activity and enhances the anticancer effects of cisplatin in non‑small cell lung cancer A549 cells via the JAK/STAT3 signaling pathway. Oncol Rep. 2019;41(3):1779–1788.30747218
   PubMed Web of Science ®Google Scholar
• JangYG, KoEB, ChoiKC. Gallic acid, a phenolic acid, hinders the progression of prostate cancer by inhibition of histone deacetylase 1 and 2 expression. J Nutr Biochem. 2020;84:108444. doi:10.1016/j.jnutbio.2020.10844432615369
   PubMed Web of Science ®Google Scholar
• HsuJD, KaoSH, OuTT, ChenYJ, LiYJ, WangCJ. Gallic acid induces G2/M phase arrest of breast cancer cell MCF-7 through stabilization of p27(Kip1) attributed to disruption of p27(Kip1)/Skp2 complex. J Agric Food Chem. 2011;59(5):1996–2003. doi:10.1021/jf103656v21299246
   PubMed Web of Science ®Google Scholar
• WangK, ZhuX, ZhangK, ZhuL, ZhouF. Investigation of gallic acid induced anticancer effect in human breast carcinoma MCF-7 cells. J Biochem Mol Toxicol. 2014;28(9):387–393. doi:10.1002/jbt.2157524864015
   PubMed Web of Science ®Google Scholar
• Ozturk SarikayaSB. Acetylcholinesterase inhibitory potential and antioxidant properties of pyrogallol. J Enzyme Inhib Med Chem. 2015;30(5):761–766. doi:10.3109/14756366.2014.96570025297710
   PubMed Web of Science ®Google Scholar
• National Toxicology Program. Toxicology and carcinogenesis studies of pyrogallol (CAS No. 87-66-1) in F344/N rats and B6C3F1/N mice (dermal studies). Natl Toxicol Program Tech Rep Ser. 2013;574:1–167.
   Google Scholar
• NicolisE, LamprontiI, DechecchiMC, et al. Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells. Int Immunopharmacol. 2008;8(12):1672–1680. doi:10.1016/j.intimp.2008.08.00118760383
   PubMed Web of Science ®Google Scholar
• KocaçalişkanI, TalanI, TerziI. Antimicrobial activity of catechol and pyrogallol as allelochemicals. Z Naturforsch C J Biosci. 2006;61(9–10):639–642. doi:10.1515/znc-2006-9-100417137106
   PubMed Web of Science ®Google Scholar
• AhnH, ImE, LeeDY, LeeHJ, JungJH, KimSH. Antitumor effect of pyrogallol via miR-134 mediated S phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling in hepatocellular carcinoma. Int J Mol Sci. 2019;20(16):3985. doi:10.3390/ijms20163985
   Web of Science ®Google Scholar
• ParkWH, ParkMN, HanYH, KimSW. Pyrogallol inhibits the growth of gastric cancer SNU-484 cells via induction of apoptosis. Int J Mol Med. 2008;22(2):263–268.18636183
   PubMed Web of Science ®Google Scholar
• RevathiS, HakkimFL, Ramesh KumarN, et al. In vivo anti cancer potential of pyrogallol in murine model of colon cancer. Asian Pac J Cancer Prev. 2019;20(9):2645–2651. doi:10.31557/APJCP.2019.20.9.264531554359
   PubMedGoogle Scholar
• YangCJ, WangCS, HungJY, et al. Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model. Lung Cancer. 2009;66(2):162–168. doi:10.1016/j.lungcan.2009.01.01619233505
   PubMed Web of Science ®Google Scholar
• Abou-ZaidMM, LombardoDA, NozzolilloC. Methyl gallate is a natural constituent of maple (Genus Acer) leaves. Nat Prod Res. 2009;23(15):1373–1377. doi:10.1080/1478641080242045719809908
   PubMed Web of Science ®Google Scholar
• ChaudhuriD, GhateNB, SinghSS, MandalN. Methyl gallate isolated from Spondias pinnata exhibits anticancer activity against human glioblastoma by induction of apoptosis and sustained extracellular signal-regulated kinase 1/2 activation. Pharmacogn Mag. 2015;11(42):269–276. doi:10.4103/0973-1296.15307825829764
   PubMed Web of Science ®Google Scholar
• MishraRK, RamakrishnaM, MishraV, et al. Pharmaco-phylogenetic investigation of methyl gallate isolated from Acacia nilotica (L.) Delile and Its cytotoxic effect on NIH3T3 mouse fibroblast. Curr Pharm Biotechnol. 2016;17(6):540–548. doi:10.2174/138920101766616012711075926813302
   PubMed Web of Science ®Google Scholar
• WangCR, ZhouR, NgTB, WongJH, QiaoWT, LiuF. First report on isolation of methyl gallate with antioxidant, anti-HIV-1 and HIV-1 enzyme inhibitory activities from a mushroom (Pholiota adiposa). Environ Toxicol Pharmacol. 2014;37(2):626–637. doi:10.1016/j.etap.2014.01.02324572641
   PubMed Web of Science ®Google Scholar
• RahmanN, JeonM, KimYS. Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion. Biofactors. 2016;42(6):716–726. doi:10.1002/biof.131027412172
   PubMed Web of Science ®Google Scholar
• KamathamS, KumarN, GudipalliP. Isolation and characterization of gallic acid and methyl gallate from the seed coats of Givotia rottleriformis Griff. and their anti-proliferative effect on human epidermoid carcinoma A431 cells. Toxicol Rep. 2015;2:520–529. doi:10.1016/j.toxrep.2015.03.00128962387
   PubMed Web of Science ®Google Scholar
• LeeH, LeeH, KwonY, et al. Methyl gallate exhibits potent antitumor activities by inhibiting tumor infiltration of CD4+CD25+ regulatory T cells. J Immunol. 2010;185(11):6698–6705. doi:10.4049/jimmunol.100137321048105
   PubMed Web of Science ®Google Scholar
• ChoiJG, KangOH, LeeYS, et al. In vitro activity of methyl gallate isolated from galla rhois alone and in combination with ciprofloxacin against clinical isolates of salmonella. J Microbiol Biotechnol. 2008;18(11):1848–1852.19047831
   PubMed Web of Science ®Google Scholar
• KaneCJ, MennaJH, SungCC, YehYC. Methyl gallate, methyl-3,4,5-trihydroxybenzoate, is a potent and highly specific inhibitor of herpes simplex virus in vitro. II. Antiviral activity of methyl gallate and its derivatives. Biosci Rep. 1988;8(1):95–102. doi:10.1007/BF011289762840133
   PubMed Web of Science ®Google Scholar
• CorreaLB, SeitoLN, ManchopeMF, et al. Methyl gallate attenuates inflammation induced by Toll-like receptor ligands by inhibiting MAPK and NF-Κb signaling pathways. Inflamm Res. 2020;69(12):1257–1270. doi:10.1007/s00011-020-01407-033037469
   PubMed Web of Science ®Google Scholar
• AsnaashariM, FarhooshR, SharifA. Antioxidant activity of gallic acid and methyl gallate in triacylglycerols of Kilka fish oil and its oil-in-water emulsion. Food Chem. 2014;159:439–444. doi:10.1016/j.foodchem.2014.03.03824767079
   PubMed Web of Science ®Google Scholar
• LiY, YaoJ, HanC, et al. Quercetin, Inflammation and Immunity. Nutrients. 2016;8(3):167. doi:10.3390/nu803016726999194
   PubMed Web of Science ®Google Scholar
• JiJJ, LinY, HuangSS, ZhangHL, DiaoYP, LiK. Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis. Afr J Tradit Complement Altern Med. 2013;10(3):418–421.24146468
   PubMedGoogle Scholar
• BuleM, AbdurahmanA, NikfarS, AbdollahiM, AminiM. Antidiabetic effect of quercetin: a systematic review and meta-analysis of animal studies. Food Chem Toxicol. 2019;125:494–502. doi:10.1016/j.fct.2019.01.03730735748
   PubMed Web of Science ®Google Scholar
• WangS, YaoJ, ZhouB, et al. Bacteriostatic effect of quercetin as an antibiotic alternative in vivo and its antibacterial mechanism in vitro. J Food Prot. 2018;81(1):68–78. doi:10.4315/0362-028X.JFP-17-21429271686
   PubMed Web of Science ®Google Scholar
• ComaladaM, CamuescoD, SierraS, et al. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur J Immunol. 2005;35(2):584–592. doi:10.1002/eji.20042577815668926
   PubMed Web of Science ®Google Scholar
• SongX, WangY, GaoL. Mechanism of antioxidant properties of quercetin and quercetin-DNA complex. J Mol Model. 2020;26(6):133. doi:10.1007/s00894-020-04356-x32399900
   PubMed Web of Science ®Google Scholar
• AlexanderSP. Flavonoids as antagonists at A1 adenosine receptors. Phytother Res. 2006;20(11):1009–1012. doi:10.1002/ptr.197517006974
   PubMed Web of Science ®Google Scholar
• YinG, WangZ, WangZ, WangX. Topical application of quercetin improves wound healing in pressure ulcer lesions. Exp Dermatol. 2018;27(7):779–786. doi:10.1111/exd.1367929733461
   PubMed Web of Science ®Google Scholar
• ZhangXA, ZhangS, YinQ, ZhangJ. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B pathway. Pharmacogn Mag. 2015;11(42):404–409. doi:10.4103/0973-1296.15309625829782
   PubMed Web of Science ®Google Scholar
• HanC, GaoH, ZhangX. Quercetin anti-cancer effect in renal cancer through regulating survivin expression and caspase 3 activity. Med One. 2016;1(1):3.
   Google Scholar
• DongY, YangJ, YangL, LiP. Quercetin inhibits the proliferation and metastasis of human non-small cell lung cancer cell line: the key role of src-mediated fibroblast growth factor-inducible 14 (Fn14)/nuclear factor kappa B (NF-κB) pathway. Med Sci Monit. 2020;26:e920537. doi:10.12659/MSM.92053732225128
   PubMed Web of Science ®Google Scholar
• OngCS, TranE, NguyenTT, et al. Quercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressions. Oncol Rep. 2004;11(3):727–733.14767529
   PubMed Web of Science ®Google Scholar
• TeekaramanD, ElayapillaiSP, ViswanathanMP, JagadeesanA. Quercetin inhibits human metastatic ovarian cancer cell growth and modulates components of the intrinsic apoptotic pathway in PA-1 cell line. Chem Biol Interact. 2019;300:91–100. doi:10.1016/j.cbi.2019.01.00830639267
   PubMed Web of Science ®Google Scholar
• AngstE, ParkJL, MoroA, et al. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas. 2013;42(2):223–229. doi:10.1097/MPA.0b013e318264ccae23000892
   PubMed Web of Science ®Google Scholar
• WardAB, MirH, KapurN, GalesDN, CarrierePP, SinghS. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J Surg Oncol. 2018;16(1):108. doi:10.1186/s12957-018-1400-z29898731
   PubMed Web of Science ®Google Scholar
• ZhangH, ZhangM, YuL, ZhaoY, HeN, YangX. Antitumor activities of quercetin and quercetin-5’,8-disulfonate in human colon and breast cancer cell lines. Food Chem Toxicol. 2012;50(5):1589–1599. doi:10.1016/j.fct.2012.01.02522310237
   PubMed Web of Science ®Google Scholar
• ChouCC, YangJS, LuHF, et al. Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells. Arch Pharm Res. 2010;33(8):1181–1191. doi:10.1007/s12272-010-0808-y20803121
   PubMed Web of Science ®Google Scholar
• ChienSY, WuYC, ChungJG, et al. Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells. Hum Exp Toxicol. 2009;28(8):493–503. doi:10.1177/096032710910700219755441
   PubMed Web of Science ®Google Scholar
• Rivera RiveraA, Castillo-PichardoL, GerenaY, DharmawardhaneS. Anti-breast cancer potential of quercetin via the Akt/AMPK/mammalian target of rapamycin (mTOR) signaling cascade. PLoS One. 2016;11(6):e0157251. doi:10.1371/journal.pone.015725127285995
   PubMed Web of Science ®Google Scholar
• SchieberM, ChandelNS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):453–462. doi:10.1016/j.cub.2014.03.034
   PubMed Web of Science ®Google Scholar
• MatésJM, SeguraJA, AlonsoFJ, MárquezJ. Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis. Arch Toxicol. 2008;82(5):273–299. doi:10.1007/s00204-008-0304-z18443763
   PubMed Web of Science ®Google Scholar
• NogueiraV, HayN. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin Cancer Res. 2013;19(16):4309–4314. doi:10.1158/1078-0432.CCR-12-142423719265
   PubMed Web of Science ®Google Scholar
• NimseSB, PalD. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015;5(35):27986–28006. doi:10.1039/C4RA13315C
   Web of Science ®Google Scholar
• BurtonGJ, JauniauxE. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2011;25(3):287–299. doi:10.1016/j.bpobgyn.2010.10.01621130690
   PubMed Web of Science ®Google Scholar
• AggarwalV, TuliHS, VarolA, et al. Role of reactive oxygen species in cancer progression: molecular mechanisms and recent advancements. Biomolecules. 2019;9(11):735. doi:10.3390/biom9110735
   PubMed Web of Science ®Google Scholar
• MatésJM, SeguraJA, AlonsoFJ, MárquezJ. Oxidative stress in apoptosis and cancer: an update. Arch Toxicol. 2012;86(11):1649–1665.22811024
   PubMed Web of Science ®Google Scholar
• StorzP. Oxidative stress and cancer. In: JakobU, ReichmannD, editors. Oxidative Stress and Redox Regulation. Berlin: Springer; 2004:427–447.
   Google Scholar
• GreenDR. Means to an End: Apoptosis and Other Cell Death Mechanisms. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2011.
   Google Scholar
• AbdullahAH, MohammedAS, RasedeeA, MirghaniMES. Oxidative stress-mediated apoptosis induced by ethanolic mango seed extract in cultured estrogen receptor positive breast cancer MCF-7 cells. Int J Mol Sci. 2015a;16(2):3528–3536. doi:10.3390/ijms1602352825664859
   PubMed Web of Science ®Google Scholar
• AbdullahAH, MohammedAS, RasedeeA, MirghaniMES, Al-QubaisiMS. Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract. BMC Compl Alternative Med. 2015b;15:45. doi:10.1186/s12906-015-0575-x
   Web of Science ®Google Scholar
• SchumackerPT. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell. 2006;10(3):175–176. doi:10.1016/j.ccr.2006.08.01516959608
   PubMed Web of Science ®Google Scholar
• StorzP. Reactive oxygen species in tumor progression. Front Biosci. 2005;10:1881–1896. doi:10.2741/166715769673
   PubMed Web of Science ®Google Scholar
• LiouGY, StorzP. Reactive oxygen species in cancer. Free Radic Res. 2010;44(5):479–496. doi:10.3109/1071576100366755420370557
   PubMed Web of Science ®Google Scholar
• Fernández-PonceMT, CasasL, MantellC. Use of high pressure techniques to produce Mangifera indica L. leaf extracts enriched in potent antioxidant phenolic compounds. Innov Food Sci Emerg Tech. 2015;29:94–106. doi:10.1016/j.ifset.2015.04.006
   Web of Science ®Google Scholar
• Fernández PonceMT, CasasL, MantellC, RodríguezM. Extraction of antioxidant compounds from different varieties of Mangifera indica leaves using green technologies. J Supercrit Fluids. 2012;72:168–175. doi:10.1016/j.supflu.2012.07.016
   Web of Science ®Google Scholar
• TyagiS, GuptaP, SainiAS, KaushalC, SharmaS. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236–240. doi:10.4103/2231-4040.9087922247890
   PubMedGoogle Scholar
• WagnerN, WagnerKD. PPAR Beta/Delta and the Hallmarks of Cancer. Cells. 2020;9(5):1133. doi:10.3390/cells9051133
   PubMed Web of Science ®Google Scholar
• TachibanaK, YamasakiD, IshimotoK, DoiT. The role of PPARs in cancer. PPAR Res. 2008;2008:102737. doi:10.1155/2008/10273718584037
   PubMed Web of Science ®Google Scholar
• AshbyJ, BradyA, ElcombeCR, et al. Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum Exp Toxicol. 1994;13(Suppl 2):S1–S117. doi:10.1177/096032719401300201
   PubMed Web of Science ®Google Scholar
• IssemannI, GreenS. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347:645–650. doi:10.1038/347645a02129546
   PubMed Web of Science ®Google Scholar
• ReddyJK, AzarnoffDL, HigniteCE. Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature. 1980;283:397–398. doi:10.1038/283397a06766207
   PubMed Web of Science ®Google Scholar
• SahaSA, KizhakepunnurLG, BahekarA, AroraRR. The role of fibrates in the prevention of cardiovascular disease—a pooled meta-analysis of long-term randomized placebo-controlled clinical trials. Am Heart J. 2007;154(5):943–953. doi:10.1016/j.ahj.2007.07.01117967602
   PubMed Web of Science ®Google Scholar
• ParkBH, VogelsteinB, KinzlerKW. Genetic disruption of PPARδ decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci U S A. 2001;98(5):2598–2603. doi:10.1073/pnas.05163099811226285
   PubMed Web of Science ®Google Scholar
• WangD, WangH, GuoY, et al. Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression. Proc Natl Acad Sci U S A. 2006;103(50):19069–19074. doi:10.1073/pnas.060794810317148604
   PubMed Web of Science ®Google Scholar
• ZuoX, PengZ, MoussalliMJ, et al. Targeted genetic disruption of peroxisome proliferator–activated receptor-δ and colonic tumorigenesis. J Natl Cancer Inst. 2009;101(10):762–767. doi:10.1093/jnci/djp07819436036
   PubMedGoogle Scholar
• HarmanFS, NicolCJ, MarinHE, WardJM, GonzalezFJ, PetersJM. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med. 2004;10(5):481–483. doi:10.1038/nm102615048110
   PubMed Web of Science ®Google Scholar
• MarinHE, PerazaMA, BillinAN, et al. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis. Cancer Res. 2006;66(8):4394–4401. doi:10.1158/0008-5472.CAN-05-427716618765
   PubMed Web of Science ®Google Scholar
• DivyaGS, MansoorKP, RasheedSP, KumarA. PPAR gamma agonists: an effective strategy for cancer treatment. J Pharm Sci Innov. 2013;2(5):1–3. doi:10.7897/2277-4572.02575
   Google Scholar
• KitamuraS, MiyazakiY, HiraokaS, et al. PPARgamma agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF-like growth factors in ras-transformed rat intestinal epithelial cells. Int J Cancer. 2001;94(3):335–342. doi:10.1002/ijc.147011745411
   PubMed Web of Science ®Google Scholar
• YangWL, FruchtH. Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis. 2001;22(9):1379–1383. doi:10.1093/carcin/22.9.137911532858
   PubMed Web of Science ®Google Scholar
• LefebvreAM, ChenI, DesreumauxP, et al. Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nature Med. 1998;4(9):1053–1057.9734399
   PubMed Web of Science ®Google Scholar
• SaezE, TontonozP, NelsonMC, et al. Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat Med. 1998;4(9):1058–1061. doi:10.1038/20429734400
   PubMed Web of Science ®Google Scholar
• XuF, NaL, LiY, ChenL. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci. 2020;10(1):54. doi:10.1186/s13578-020-00416-032266056
   PubMed Web of Science ®Google Scholar
• HemmingsBA, RestucciaDF. PI3K-PKB/Akt Pathway. Cold Spring Harb Perspect Biol. 2012;4(9):a011189. doi:10.1101/cshperspect.a01118922952397
   PubMed Web of Science ®Google Scholar
• OrtegaMA, Fraile-MartínezO, AsúnsoloA, BujánJ, García-HonduvillaN, CocaS. Signal transduction pathways in breast cancer: the important role of PI3K/Akt/mTOR. J Oncol. 2020;2020:9258396. doi:10.1155/2020/925839632211045
   PubMed Web of Science ®Google Scholar
• PaplomataE, O’ReganR. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther Adv Med Oncol. 2014;6(4):154–166. doi:10.1177/175883401453002325057302
   PubMed Web of Science ®Google Scholar
• LiuR, ChenY, LiuG, et al. PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers. Cell Death Dis. 2020;11(9):797. doi:10.1038/s41419-020-02998-632973135
   PubMed Web of Science ®Google Scholar
• BrownKK, TokerA. The phosphoinositide 3-kinase pathway and therapy resistance in cancer. F1000Prime Rep. 2015;7:13. doi:10.12703/P7-1325750731
   PubMedGoogle Scholar
• WilksST. Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway. Breast. 2015;24(5):548–555. doi:10.1016/j.breast.2015.06.00226187798
   PubMed Web of Science ®Google Scholar
• LiS, PatelDJ. Drosha and dicer: slicers cut from the same cloth. Cell Res. 2016;26(5):511–512. doi:10.1038/cr.2016.1927125999
   PubMed Web of Science ®Google Scholar
• DongY, FuC, GuanH, ZhangZ, ZhouT, LiB. Prognostic significance of miR-126 in various cancers: a meta-analysis. Onco Targets Ther. 2016;9:2547–2555. doi:10.2147/OTT.S10348127217773
   PubMed Web of Science ®Google Scholar
• MeisterJ, SchmidtMHH. miR-126 and miR-126*: new Players in Cancer. ScientificWorldJournal. 2010;10:2090–2100. doi:10.1100/tsw.2010.19820953557
   PubMed Web of Science ®Google Scholar
• TavazoieSF, AlarcónC, OskarssonT, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–152. doi:10.1038/nature0648718185580
   PubMed Web of Science ®Google Scholar
• WangCZ, YuanP, LiY. MiR-126 regulated breast cancer cell invasion by targeting ADAM9. Int J Clin Exp Pathol. 2015;8(6):6547–6553.26261534
   PubMed Web of Science ®Google Scholar
• ChumsriS, HowesT, BaoT, SabnisG, BrodieA. Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol. 2011;125(1–2):13–22. doi:10.1016/j.jsbmb.2011.02.00121335088
   PubMed Web of Science ®Google Scholar
• Saha RoyS, VadlamudiRK. Role of estrogen receptor signaling in breast cancer metastasis. Int J Breast Cancer. 2012;2012:654698. doi:10.1155/2012/65469822295247
   PubMedGoogle Scholar
• ChumsriS. Clinical utilities of aromatase inhibitors in breast cancer. Int J Womens Health. 2015;7:493–499. doi:10.2147/IJWH.S6990726005359
   PubMedGoogle Scholar
• ZhaoH, InnesJ, BrooksDC, et al. A novel promoter controls Cyp19a1 gene expression in mouse adipose tissue. Reprod Biol Endocrinol. 2009;7(1):37. doi:10.1186/1477-7827-7-3719393092
   PubMed Web of Science ®Google Scholar
• ZhaoH, ZhouL, ShangguanAJ, BulunSE. Aromatase expression and regulation in breast and endometrial cancer. J Mol Endocrinol. 2016;57(1):R19–R33. doi:10.1530/JME-15-031027067638
   PubMed Web of Science ®Google Scholar
• ChenS, ZhouD, OkuboT, et al. Prevention and treatment of breast cancer by suppressing aromatase activity and expression. Ann N Y Acad Sci. 2002;963(1):229–238. doi:10.1111/j.1749-6632.2002.tb04115.x12095949
   PubMed Web of Science ®Google Scholar
• SunF, XuX, WangX, ZhangB. Regulation of autophagy by Ca2+ . Tumour Biol. 2016;37(12):15467–15476. doi:10.1007/s13277-016-5353-y
   Google Scholar
• MachacaK. Ca2+ signaling, genes and the cell cycle. Cell Calcium. 2010;48(5):243–250. doi:10.1016/j.ceca.2010.10.00321084120
   PubMed Web of Science ®Google Scholar
• PintonP, GiorgiC, SivieroR, ZecchiniE, RizzutoR. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 2008;27(50):6407–6418. doi:10.1038/onc.2008.30818955969
   PubMed Web of Science ®Google Scholar
• TonelliFMP, SantosAK, GomesDA, et al. Stem cells and calcium signaling. Adv Exp Med Biol. 2012;740:891–916.22453975
   PubMed Web of Science ®Google Scholar
• BaranI. Calcium and cell cycle progression: possible effects of external perturbations on cell proliferation. Biophys J. 1996;70(3):1198–1213. doi:10.1016/S0006-3495(96)79679-08785278
   PubMed Web of Science ®Google Scholar
• IamshanovaO, Fiorio PlaA, PrevarskayaN. Molecular mechanisms of tumour invasion: regulation by calcium signals. J Physiol. 2017;595(10):3063–3075. doi:10.1113/JP27284428304082
   PubMed Web of Science ®Google Scholar
• RimessiA, PedrialiG, VezzaniB, et al. Interorganellar calcium signaling in the regulation of cell metabolism: a cancer perspective. Semin Cell Dev Biol. 2020;98:167–180.31108186
   PubMed Web of Science ®Google Scholar
• TsaiFC, KuoGH, ChangSW, TsaiPJ. Ca2+ signaling in cytoskeletal reorganization, cell migration, and cancer metastasis. Biomed Res Int. 2015;2015:409245. doi:10.1155/2015/40924525977921
   PubMed Web of Science ®Google Scholar
• VilborgA, PassarelliMC, SteitzJA. Calcium signaling and transcription: elongation, DoGs, and eRNAs. Receptors Clin Investig. 2016;3(1):e1169.
   Google Scholar
• PrattSJP, Hernández-OchoaE, MartinSS. Calcium signaling: breast cancer’s approach to manipulation of cellular circuitry. Biophys Rev. 2020;12(6):1343–1359. doi:10.1007/s12551-020-00771-933569087
   PubMedGoogle Scholar
• BootmanMD. Calcium signaling. Cold Spring Harb Perspect Biol. 2012;4(7):a011171. doi:10.1101/cshperspect.a01117122751152
   PubMed Web of Science ®Google Scholar
• YáñezM, Gil-LongoJ, Campos-ToimilM. Calcium binding proteins. Adv Exp Med Biol. 2012;740:461–482.22453954
   PubMed Web of Science ®Google Scholar
• SoCL, SaunusJM, Roberts-ThomsonSJ, MonteithGR. Calcium signalling and breast cancer. Semin Cell Dev Biol. 2019;94:74–83. doi:10.1016/j.semcdb.2018.11.00130439562
   PubMed Web of Science ®Google Scholar
• GhoshS, MayMJ, KoppEB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16(1):225–260. doi:10.1146/annurev.immunol.16.1.2259597130
   PubMed Web of Science ®Google Scholar
• WangW, NagSA, ZhangR. Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr Med Chem. 2015;22(2):264–289. doi:10.2174/092986732166614110612431525386819
   PubMed Web of Science ®Google Scholar
• GhoshG, WangVY, HuangDB, FuscoA. NF-κB regulation: lessons from structures. Immunol Rev. 2012;246(1):36–58. doi:10.1111/j.1600-065X.2012.01097.x22435546
   PubMed Web of Science ®Google Scholar
• O’DeaE, HoffmannA. NF-κB signaling. Wiley Interdiscip Rev Syst Biol Med. 2009;1(1):107. doi:10.1002/wsbm.3020151024
   PubMed Web of Science ®Google Scholar
• LiuT, ZhangL, JooD, SunSC. NF-κB signaling in inflammation Signal Transduct Target Ther. Signal Transduct Targeted Therapy. 2017;2:17023.
   PubMed Web of Science ®Google Scholar
• ParkYH. The nuclear factor-kappa B pathway and response to treatment in breast cancer. Pharmacogenomics. 2017;18(18):1697–1709. doi:10.2217/pgs-2017-004429182047
   PubMed Web of Science ®Google Scholar
• HuberMA, AzoiteiN, BaumannB, et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569–581. doi:10.1172/JCI20042135815314694
   PubMed Web of Science ®Google Scholar
• KhongthongP, RoseweirAK, EdwardsJ. The NF-KB pathway and endocrine therapy resistance in breast cancer. Endocr Relat Cancer. 2019;26(6):R369–R380. doi:10.1530/ERC-19-008732013374
   PubMed Web of Science ®Google Scholar
• LiF, SethiG. Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta. 2010;1805(2):167–180.20079806
   PubMed Web of Science ®Google Scholar
• ShibataA, NagayaT, ImaiT, FunahashiH, NakaoA, SeoH. Inhibition of NF-κB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells. Breast Cancer Res Treat. 2002;73(3):237–243. doi:10.1023/A:101587253167512160329
   PubMed Web of Science ®Google Scholar
• XiaY, ShenS, VermaIM. NF-κB, an active player in human cancers. Cancer Immunol Res. 2014;2(9):823–830. doi:10.1158/2326-6066.CIR-14-011225187272
   PubMed Web of Science ®Google Scholar
• BaudV, KarinM. Is NF-κB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 2009;8(1):33–40. doi:10.1038/nrd278119116625
   PubMed Web of Science ®Google Scholar
• ViatourP, MervilleMP, BoursV, ChariotA. Phosphorylation of NF-kB and IkB proteins: implications in cancer and inflammation. Trends Biochem Sci. 2005;30(1):43–52. doi:10.1016/j.tibs.2004.11.00915653325
   PubMed Web of Science ®Google Scholar
• SarkarA, SreenivasanY, RameshGT, MannaSK. beta-D-Glucoside suppresses tumor necrosis factor-induced activation of nuclear transcription factor kappaB but potentiates apoptosis. J Biol Chem. 2004;279(32):33768–33781. doi:10.1074/jbc.M40342420015161907
   PubMed Web of Science ®Google Scholar
• KomiyaY, HabasR. Wnt signal transduction pathways. Organogenesis. 2008;4(2):68–75. doi:10.4161/org.4.2.585119279717
   PubMedGoogle Scholar
• HeX, SemenovM, TamaiK, ZengX. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way. Development. 2004;131(8):1663–1677. doi:10.1242/dev.0111715084453
   PubMed Web of Science ®Google Scholar
• MacDonaldBT, TamaiK, HeX. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26. doi:10.1016/j.devcel.2009.06.01619619488
   PubMed Web of Science ®Google Scholar
• KhalafAM, FuentesD, MorshidAI, et al. Role of Wnt/β-catenin signaling in hepatocellular carcinoma, pathogenesis, and clinical significance. J Hepatocell Carcinoma. 2018;5:61–73. doi:10.2147/JHC.S15670129984212
   PubMed Web of Science ®Google Scholar
• SethiJK, Vidal-PuigA. Wnt signalling and the control of cellular metabolism. Biochem J. 2010;427(1):1–17. doi:10.1042/BJ2009186620226003
   PubMed Web of Science ®Google Scholar
• RenL, ChenH, SongJ, et al. MiR-454-3p-mediated Wnt/β-catenin signaling antagonists suppression promotes breast cancer metastasis. Theranostics. 2019;9(2):449–465. doi:10.7150/thno.2905530809286
   PubMed Web of Science ®Google Scholar
• ArendRC, Londoño-JoshiAI, StraughnJMJ, BuchsbaumDJ. The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013;131(3):772–779. doi:10.1016/j.ygyno.2013.09.03424125749
   PubMed Web of Science ®Google Scholar
• DeP, CarlsonJH, WuH, MarcusA, Leyland-JonesB, DeyN. Wnt-beta-catenin pathway signals metastasis-associated tumor cell phenotypes in triple negative breast cancers. Oncotarget. 2016;7(28):43124–43149. doi:10.18632/oncotarget.898827281609
   PubMedGoogle Scholar
• QuB, LiuBR, DuYJ, et al. Wnt/β-catenin signaling pathway may regulate the expression of angiogenic growth factors in hepatocellular carcinoma. Oncol Lett. 2014;7(4):1175–1178. doi:10.3892/ol.2014.182824944688
   PubMed Web of Science ®Google Scholar
• JangGB, KimJY, ChoSD, et al. Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype. Sci Rep. 2015;5(1):12465. doi:10.1038/srep1246526202299
   PubMed Web of Science ®Google Scholar
• DeBose-BoydRA. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 2008;18(6):609–621. doi:10.1038/cr.2008.6118504457
   PubMed Web of Science ®Google Scholar
• DaniloC, FrankPG. Cholesterol and breast cancer development. Curr Opin Pharmacol. 2012;12(6):677–682. doi:10.1016/j.coph.2012.07.00922867847
   PubMed Web of Science ®Google Scholar
• SantosCR, DominguesG, MatiasI, et al. LDL-cholesterol signaling induces breast cancer proliferation and invasion. Lipids Health Dis. 2014;13(1):16. doi:10.1186/1476-511X-13-1624428917
   PubMed Web of Science ®Google Scholar
• StancuC, SimaA. Statins: mechanism of action and effects. J Cell Mol Med. 2001;5(4):378–387. doi:10.1111/j.1582-4934.2001.tb00172.x12067471
   PubMed Web of Science ®Google Scholar
• BorgquistS, BjarnadottirO, KimbungS, AhernTP. Statins: a role in breast cancer therapy?J Intern Med. 2018;284(4):346–357. doi:10.1111/joim.1280629923256
   PubMed Web of Science ®Google Scholar
• HuangQ, Figueiredo-PereiraME. Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications. Apoptosis. 2010;15(11):1292–1311.20131003
   PubMed Web of Science ®Google Scholar
• CrawfordLJ, WalkerB, IrvineAE. Proteasome inhibitors in cancer therapy. J Cell Commun Signal. 2011;5(2):101–110. doi:10.1007/s12079-011-0121-721484190
   PubMed Web of Science ®Google Scholar
• AgyinJK, SanthammaB, NairHB, RoySS, TekmalRR. BU-32: a novel proteasome inhibitor for breast cancer. Breast Cancer Res. 2009;11(5):R74. doi:10.1186/bcr241119821999
   PubMed Web of Science ®Google Scholar
• JonesMD, LiuJC, BarthelTK, et al. A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes. Clin Cancer Res. 2010;16(20):4978–4989. doi:10.1158/1078-0432.CCR-09-329320843837
   PubMed Web of Science ®Google Scholar
• ShinoharaK, TomiokaM, NakanoH, TonéS, ItoH, KawashimaS. Apoptosis induction resulting from proteasome inhibition. Biochem J. 1996;317(Pt 2):385–388. doi:10.1042/bj31703858713062
   PubMed Web of Science ®Google Scholar
• van der VormLN, RemijnJA, de LaatB, HuskensD. Effects of plasmin on von Willebrand factor and platelets: a narrative review. TH Open. 2018;2(2):e218–e228.31249945
   PubMedGoogle Scholar
• DidiasovaM, WujakL, WygreckaM, ZakrzewiczD. From plasminogen to plasmin: role of plasminogen receptors in human cancer. Int J Mol Sci. 2014;15(11):21229–21252. doi:10.3390/ijms15112122925407528
   PubMed Web of Science ®Google Scholar
• SwedbergJE, HarrisJM. Natural and engineered plasmin inhibitors: applications and design strategies. Chembiochem. 2012;13(3):336–348. doi:10.1002/cbic.20110067322238174
   PubMed Web of Science ®Google Scholar
• CastellinoFJ, PloplisVA. Structure and function of the plasminogen/plasmin system. Thromb Haemost. 2005;93(4):647–654. doi:10.1160/TH04-12-084215841308
   PubMed Web of Science ®Google Scholar
• DeryuginaEI, QuigleyJP. Cell surface remodeling by plasmin: a new function for an old enzyme. J Biomed Biotechnol. 2012;2012:564259. doi:10.1155/2012/56425923097597
   PubMed Web of Science ®Google Scholar
• HayashidoY, HamanaT, YoshiokaY, KitanoH, KoizumiK, OkamotoT. Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin. Int J Oncol. 2005;27(3):693–698.16077918
   PubMed Web of Science ®Google Scholar
• SpieringD, HodgsonL. Dynamics of the Rho-family small GTPases in actin regulation and motility. Cell Adh Migr. 2011;5(2):170–180. doi:10.4161/cam.5.2.1440321178402
   PubMed Web of Science ®Google Scholar
• AlgayadhIG, DronamrajuV, SylvesterPW. Role of Rac1/WAVE2 signaling in mediating the inhibitory effects of γ-tocotrienol on mammary cancer cell migration and invasion. Biol Pharm Bull. 2016;39(12):1974–1982. doi:10.1248/bpb.b16-0046127904039
   PubMed Web of Science ®Google Scholar
• BompardG, CaronE. Regulation of WASP/WAVE proteins: making a long story short. J Cell Biol. 2004;166(7):957–962. doi:10.1083/jcb.20040312715452139
   PubMed Web of Science ®Google Scholar
• KurisuS, TakenawaT. WASP and WAVE family proteins: friends or foes in cancer invasion?Cancer Sci. 2010;101(10):2093–2104. doi:10.1111/j.1349-7006.2010.01654.x20707804
   PubMed Web of Science ®Google Scholar
• FernandoHS, DaviesSR, ChhabraA, et al. Expression of the WASP verprolin-homologues (WAVE members) in human breast cancer. Oncology. 2007;73(5–6):376–383. doi:10.1159/00013615718509249
   PubMed Web of Science ®Google Scholar
• PorterBA, OrtizMA, BratslavskyG, KotulaL. Structure and function of the nuclear receptor superfamily and current targeted therapies of prostate cancer. Cancers. 2019;11(12):1852. doi:10.3390/cancers11121852
   Web of Science ®Google Scholar
• BjörnströmL, SjöbergM. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 2005;19(4):833–842. doi:10.1210/me.2004-048615695368
   PubMedGoogle Scholar
• AcconciaF, KumarR. Signaling regulation of genomic and nongenomic functions of estrogen receptors. Cancer Lett. 2006;238(1):1–14. doi:10.1016/j.canlet.2005.06.01816084012
   PubMed Web of Science ®Google Scholar
• VrtačnikP, OstanekB, Mencej-BedračS, MarcJ. The many faces of estrogen signaling. Biochem Med (Zagreb). 2014;24(3):329–342. doi:10.11613/BM.2014.03525351351
   PubMed Web of Science ®Google Scholar
• WilliamsC, LinCY. Oestrogen receptors in breast cancer: basic mechanisms and clinical implications. Ecancermedicalscience. 2013;7(1):370.24222786
   PubMedGoogle Scholar
• HartmanJ, GustafssonJA. Estrogen receptor beta in breast cancer–diagnostic and therapeutic implications. Steroids. 2009;74(8):635–641. doi:10.1016/j.steroids.2009.02.00519463683
   PubMed Web of Science ®Google Scholar
• PowellE, ShanleE, BrinkmanA, et al. Identification of estrogen receptor dimer selective ligands reveals growth-inhibitory effects on cells that co-express ERα and ERβ. PLoS One. 2012;7(2):e30993. doi:10.1371/journal.pone.003099322347418
   PubMed Web of Science ®Google Scholar
• SanzP. AMP-activated protein kinase: structure and regulation. Curr Protein Pept Sci. 2008;9(5):478–492. doi:10.2174/13892030878591525418855699
   PubMed Web of Science ®Google Scholar
• MihaylovaMM, ShawRJ. The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism. Nat Cell Biol. 2011;13(9):1016–1023. doi:10.1038/ncb232921892142
   PubMed Web of Science ®Google Scholar
• XuQ, SiLY. Protective effects of AMP-activated protein kinase in the cardiovascular system. J Cell Mol Med. 2010;14(11):2604–2613. doi:10.1111/j.1582-4934.2010.01179.x20874722
   PubMed Web of Science ®Google Scholar
• HinchyEC, GruszczykAV, WillowsR, et al. Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem. 2018;293(44):17208–17217. doi:10.1074/jbc.RA118.00257930232152
   PubMed Web of Science ®Google Scholar
• RabinovitchRC, SamborskaB, FaubertB, et al. AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep. 2017;21(1):1–9. doi:10.1016/j.celrep.2017.09.02628978464
   PubMed Web of Science ®Google Scholar
• WangS, SongP, ZouMH. AMP-activated protein kinase, stress responses and cardiovascular diseases. Clin Sci (Lond). 2012;122(12):555–573. doi:10.1042/CS2011062522390198
   PubMed Web of Science ®Google Scholar
• YiY, ChenD, AoJ, et al. Transcriptional suppression of AMPKα1 promotes breast cancer metastasis upon oncogene activation. Proc Natl Acad Sci U S A. 2020;117(14):8013–8021. doi:10.1073/pnas.191478611732193335
   PubMed Web of Science ®Google Scholar
• FoxMM, PhoenixKN, KopsiaftisSG, ClaffeyKP. AMP-activated protein kinase α 2 isoform suppression in primary breast cancer alters AMPK growth control and apoptotic signaling. Genes Cancer. 2013;4(1–2):3–14. doi:10.1177/194760191348634623946867
   PubMedGoogle Scholar
• JhaveriTZ, WooJ, ShangX, ParkBH, GabrielsonE. AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer. Oncotarget. 2015;6(17):14754–14765. doi:10.18632/oncotarget.447426143491
   PubMedGoogle Scholar
• ZouYF, XieCW, YangSX, XiongJP. AMPK activators suppress breast cancer cell growth by inhibiting DVL3-facilitated Wnt/β-catenin signaling pathway activity. Mol Med Rep. 2017;15(2):899–907. doi:10.3892/mmr.2016.609428035400
   PubMed Web of Science ®Google Scholar
• Ben-SahraI, DiratB, LaurentK, et al. Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death. Cell Death Differ. 2013;20(4):611–619. doi:10.1038/cdd.2012.15723238567
   PubMed Web of Science ®Google Scholar
• KimSH, ParkS, YuHS, KoKH, ParkHG, KimYS. The antipsychotic agent clozapine induces autophagy via the AMPK-ULK1-Beclin1 signaling pathway in the rat frontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:96–104. doi:10.1016/j.pnpbp.2017.10.01229079139
   PubMed Web of Science ®Google Scholar
• VermeulenK, Van BockstaeleDR, BernemanZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131–149. doi:10.1046/j.1365-2184.2003.00266.x12814430
   PubMed Web of Science ®Google Scholar
• CasimiroMC, CrosariolM, LoroE, LiZ, PestellRG. Cyclins and cell cycle control in cancer and disease. Genes Cancer. 2012;3(11–12):649–657. doi:10.1177/194760191347902223634253
   PubMedGoogle Scholar
• TopacioBR, ZatulovskiyE, CristeaS, et al. Cyclin D-Cdk4,6 drives cell-cycle progression via the retinoblastoma protein’s c-terminal helix. Mol Cell. 2019;74(4):758–770. doi:10.1016/j.molcel.2019.03.02030982746
   PubMed Web of Science ®Google Scholar
• BertoliC, SkotheimJM, de BruinRA. Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol. 2013;14(8):518–528. doi:10.1038/nrm362923877564
   PubMed Web of Science ®Google Scholar
• VoellerD, RahmanL, Zajac-KayeM. Elevated levels of thymidylate synthase linked to neoplastic transformation of mammalian cells. Cell Cycle. 2004;3(8):1005–1007. doi:10.4161/cc.3.8.106415280655
   PubMed Web of Science ®Google Scholar
• NarasimhaAM, KaulichM, ShapiroGS, ChoiYJ, SicinskiP, DowdySF. Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. eLife. 2014;3:e02872. doi:10.7554/eLife.02872
   PubMed Web of Science ®Google Scholar
• Lara-GonzalezP, MoyleMW, BudrewiczJ, Mendoza-LopezJ, OegemaK, DesaiA. The G2-to-M transition is ensured by a dual mechanism that protects cyclin B from degradation by Cdc20-activated APC/C. Dev Cell. 2019;51(3):313–325. doi:10.1016/j.devcel.2019.09.00531588029
   PubMed Web of Science ®Google Scholar
• TavakolianS, GoudarziH, FaghihlooE. Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers. Infect Agent Cancer. 2020;15:27. doi:10.1186/s13027-020-00295-732377232
   PubMed Web of Science ®Google Scholar
• ThuKL, Soria-BretonesI, MakTW, CesconDW. Targeting the cell cycle in breast cancer: towards the next phase. Cell Cycle. 2018;17(15):1871–1885. doi:10.1080/15384101.2018.150256730078354
   PubMed Web of Science ®Google Scholar
• The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61–70. doi:10.1038/nature1141223000897
   PubMed Web of Science ®Google Scholar