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Review Articles

Plant-based natural products in cancer therapeutics

, , , , , , & show all
Pages 365-380 | Received 28 Jun 2023, Accepted 21 Jan 2024, Published online: 28 Feb 2024

References

  • Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2(8):563–572. doi: 10.1038/nrc865.
  • Tarin D. Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance. Semin Cancer Biol. 2011;21(2):72–82. doi: 10.1016/j.semcancer.2010.12.006.
  • Ali Abdalla YO, Subramaniam B, Nyamathulla S, et al. Natural products for cancer therapy: a review of their mechanism of actions and toxicity in the past decade. J Trop Med. 2022;2022:5794350–5794320. doi: 10.1155/2022/5794350.
  • Zhang Y, Li Z, Huang Y, et al. Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia. Front Immunol. 2023;14(1):1–18. doi: 10.3389/fimmu.2023.1258786.
  • Yang Y, Li Z, Li Y, et al. Relapsed/refractory diffuse large B cell lymphoma with cardiac involvement: a case report and literature review. Front Oncol. 2023;13:1–8. doi: 10.3389/fonc.2023.1091074.
  • Davis E, Oh B, Butow P, et al. Cancer patient disclosure and patient-doctor communication of complementary and alternative medicine use: a systematic review. Forsch Komplementarmed. 2014;21(1):58–59.
  • Harvey A, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015;14(2):111–129. doi: 10.1038/nrd4510.
  • ChongZhi W, Hui H, XiaoYu W, et al. Trends in scientific publications of Chinese medicine. Am J Chin Med. 2012;40(6):1123–1141.
  • Bell RM. A review of complementary and alternative medicine practices among cancer survivors. Clin J Oncol Nurs. 2010;14(3):365–370. doi: 10.1188/10.CJON.365-370.
  • Hait WN. Forty years of translational cancer research. Cancer Discov. 2011;1(5):383–390. doi: 10.1158/2159-8290.CD-11-0196.
  • Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009;109(7):3012–3043. doi: 10.1021/cr900019j.
  • Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386. doi: 10.1002/ijc.29210.
  • Ruela-de-Sousa RR, Fuhler GM, Blom N, et al. Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy. Cell Death Dis. 2010;1(1):e19. doi: 10.1038/cddis.2009.18.
  • Cao X, Liu B, Cao W, et al. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells. Chin J Cancer Res. 2013;25(6):212–222. doi: 10.3978/j.issn.1000-9604.2013.04.01.
  • Wang Q, Zeng P, Liu Y, et al. Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis. Int Immunopharmacol. 2015;27(1):24–31. doi: 10.1016/j.intimp.2015.04.018.
  • Gupta S, Afaq F, Mukhtar H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene. 2002;21(23):3727–3738. doi: 10.1038/sj/onc/1205474.
  • Seo H-S, Jo JK, Ku JM, et al. Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells. Biosci Rep. 2015;35:1–14. doi: 10.1042/BSR20150165.
  • Zhou Z, Tang M, Liu Y, et al. Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line. Anticancer Drugs. 2017;28(4):446–456. doi: 10.1097/CAD.0000000000000479.
  • Maggioni D, Garavello W, Rigolio R, et al. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol. 2013;43(5):1675–1682. doi: 10.3892/ijo.2013.2072.
  • Fang JIN, Bao YY, Zhou SH, et al. Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression of glucose transporter-1. Mol Med Rep. 2015;12(5):6461–6466. doi: 10.3892/mmr.2015.4233.
  • Zhao G, Han X, Cheng W, et al. Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells. Oncol Rep. 2017;37(4):2277–2285. doi: 10.3892/or.2017.5450.
  • Barzegar E, Fouladdel S, Movahhed TK, et al. Effects of berberine on proliferation, cell cycle distribution and apoptosis of human breast cancer T47D and MCF7 cell lines. Iran J Basic Med Sci. 2015;18(4):334–342. doi: 10.22038/ijbms.2015.4281.
  • Ahmadiankia N, Moghaddam HK, Mishan MA, et al. Berberine suppresses migration of MCF-7 breast cancer cells through down-regulation of chemokine receptors. Iran J Basic Med Sci. 2016;19(2):125–131. doi: 10.22038/ijbms.2016.6531.
  • Chen J, Wu F-X, Luo H-L, et al. Berberine upregulates miR-22-3p to suppress hepatocellular carcinoma cell proliferation by targeting Sp1. Am J Transl Res. 2016;8(11):4932–4941.
  • Eom K-S, Hong J-M, Youn M-J, et al. Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway. Biol Pharm Bull. 2008;31(4):558–562. doi: 10.1248/bpb.31.558.
  • Zou K, Li Z, Zhang Y, et al. Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol Sin. 2017;38(2):157–167. doi: 10.1038/aps.2016.125.
  • Kondo T, Oka T, Sato H, et al. Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development. Int J Oncol. 2009;35(23):547–557. doi: 10.3892/ijo.
  • Kwon HJ, Shim JS, Kim JH, et al. Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells. Jpn J Cancer Res. 2002;93(4):417–425. doi: 10.1111/j.1349-7006.2002.tb01273.x.
  • Sawada N, Kataoka K, Kondo K, et al. Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice. Br J Cancer. 2004;90(8):1672–1678. doi: 10.1038/sj.bjc.6601746.
  • Ehrhardt H, Fulda S, Führer M, et al. Betulinic acid-induced apoptosis in leukemia cells. Leukemia. 2004;18(8):1406–1412. doi: 10.1038/sj.leu.2403406.
  • Wick W, Grimmel C, Wagenknecht B, et al. Betulinic acid-induced apoptosis in glioma cells: a sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J Pharmacol Exp Ther. 1999;289(3):1306–1312.
  • Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout. Clin Ther. 2014;36(10):1465–1479. doi: 10.1016/j.clinthera.2014.07.017.
  • Leung YY, Li L, Hui Y, et al. HHS public access. Semin Arthritis Rheum. 2016;45(3):341–350. doi: 10.1016/j.semarthrit.2015.06.013.Colchicine.
  • Cho JH, Joo YH, Shin EY, et al. Anticancer effects of colchicine on hypopharyngeal cancer. Anticancer Res. 2017;37:6269–6280. doi: 10.21873/anticanres.12078.
  • Zhang T, Chen W, Jiang X, et al. Anticancer effects and underlying mechanism of colchicine on human gastric cancer cell lines in vitro and in vivo. Biosci Rep. 2019;39(1):1–10.
  • Herbst JJ, Hurwitz R, Sunshine P, et al. Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal. J Clin Invest. 1970;49(3):530–536. doi: 10.1172/JCI106263.
  • Sun M, Estrov Z, Ji Y, et al. Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther. 2008;7(3):464–473. doi: 10.1158/1535-7163.MCT-07-2272.
  • Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol. 2003;171(7):3863–3871. doi: 10.4049/jimmunol.171.7.3863.
  • Wu L, Guo L, Liang Y, et al. Curcumin suppresses stem-like traits of lung cancer cells via inhibiting the JAK2/STAT3 signaling pathway. Oncol Rep. 2015;34(6):3311–3317. doi: 10.3892/or.2015.4279.
  • Cai X-Z, Wang J, Xiao-Dong L, et al. Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther. 2009;8(14):1360–1368. doi: 10.4161/cbt.8.14.8720.
  • Dou H, Shen R, Tao J, et al. Curcumin suppresses the colon cancer proliferation by inhibiting Wnt/β-catenin pathways via miR-130a. Front Pharmacol. 2017;8:1–9. doi: 10.3389/fphar.2017.00877.
  • Karavasili C, Andreadis DA, Katsamenis OL, et al. Synergistic antitumor potency of a self-assembling peptide hydrogel for the local co-delivery of doxorubicin and curcumin in the treatment of head and neck cancer. Mol Pharm. 2019;16(6):2326–2341. doi: 10.1021/acs.molpharmaceut.8b01221.
  • Liu Q, Loo WTY, Sze SCW, et al. Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFκB, cyclinD and MMP-1 transcription. Phytomedicine. 2009;16(10):916–922. doi: 10.1016/j.phymed.2009.04.008.
  • Huang AC, Lin SY, Su CC, et al. Effects of curcumin on N-bis(2-hydroxypropyl) nitrosamine (DHPN)-induced lung and liver tumorigenesis in BALB/c mice in vivo. In Vivo. 2008;22(6):781–786.
  • Cao J, Jia L, Zhou HM, et al. Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicol Sci. 2006;91(2):476–483. doi: 10.1093/toxsci/kfj153.
  • Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491–4499. doi: 10.1158/1078-0432.CCR-08-0024.
  • Li X, Lu J, Kan Q, et al. Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells. Sci Rep. 2017;7(1):1–20. doi: 10.1038/s41598-017-05086-6.
  • Gojo I, Zhang B, Fenton RG. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of mcl-1. Clin Cancer Res. 2002;8(11):3527–3538.
  • Alonso M, Tamasdan C, Miller DC, et al. Flavopiridol induces apoptosis in glioma cell lines independent of retinoblastoma and p53 tumor suppressor pathway alterations by a caspase-independent pathway. Mol Cancer Ther. 2003;2(2):139–150.
  • Shapiro GI, Koestner DA, Matranga CB, et al. Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res. 1999;5(10):2925–2938.
  • Wirger A, Perabo FGE, Burgemeister S, et al. Flavopiridol, an inhibitor of cyclin-dependent kinases, induces growth inhibition and apoptosis in bladder cancer cells in vitro and in vivo. Anticancer Res. 2005;25(6):4341–4347.
  • Fujita KI, Kubota Y, Ishida H, et al. Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. WJG. 2015;21(43):12234–12248. doi: 10.3748/wjg.v21.i43.12234.
  • Rougier P, Cutsem VE, Bajetta E, et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet. 1998;352(9138):1407–1412. doi: 10.1016/S0140-6736(98)03085-2.
  • Perez EA, Hillman DW, Mailliard JA, et al. Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both. J Clin Oncol. 2004;22(14):2849–2855. doi: 10.1200/JCO.2004.10.047.
  • Suzumiya J, Suzushima H, Maeda K, et al. Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma. Int J Hematol. 2004;79(3):266–270. doi: 10.1532/IJH97.03071.
  • Wiseman LR, Markham A. A review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer. Drugs. 1996;52(4):606–623. doi: 10.2165/00003495-199652040-00013.
  • Imran M, Salehi B, Sharifi-Rad J, et al. Kaempferol: a key emphasis to its anticancer potential. Molecules. 2019;24(12):2277. doi: 10.3390/molecules24122277.
  • Nguyen TTT, Tran E, Ong CK. Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. 2003;121:110–121. doi: 10.1002/jcp.10340.
  • Kim S, Choi K. Anti-cancer effect and underlying mechanism (s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol Res. 2013;29(4):229–234. doi: 10.5487/TR.2013.29.4.229.
  • Lee J, Kim JH. Kaempferol inhibits pancreatic cancer cell growth and migration through the blockade of EGFR-related pathway in vitro. PLoS One. 2016;11(5):e0155264. doi: 10.1371/journal.pone.0155264.
  • Song W, Dang Q, Xu D, et al. Kaempferol induces cell cycle arrest and apoptosis in renal cell carcinoma through EGFR/p38 signaling. Oncol Rep. 2014;31(3):1350–1356. doi: 10.3892/or.2014.2965.
  • Halimah E, Diantini A, Destiani DP, et al. Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines. Biomed Rep. 2015;3(1):115–117. doi: 10.3892/br.2014.385.
  • Lee G, Choi K, Hwang K. Kaempferol a phytoestrogen suppressed triclosan-induced epithelial mesenchymal transition and metastatic related behaviors of MCF-7 breast cancer cells. Environ Toxicol Pharmacol. 2017;49:48–57. doi: 10.1016/j.etap.2016.11.016.
  • Zhang C, Sheng J, Li G, et al. Effects of berberine and its derivatives on cancer a systems pharmacology review. Front Pharmacol. 2020;10:1–10. doi: 10.3389/fphar.2019.01461.
  • Bai Y, Mao Q, Qin J, et al. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci. 2010;101(2):488–493. doi: 10.1111/j.1349-7006.2009.01415.x.
  • Roy SK, Chen Q, Fu J, et al. Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors. PLoS One. 2011;6(9):e25166. doi: 10.1371/journal.pone.0025166.
  • Bishayee A, Barnes KF, Bhatia D, et al. Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis. Cancer Prev Res. 2010;3(6):753–763. doi: 10.1158/1940-6207.CAPR-09-0171.
  • Tessitore L, Davit A, Sarotto I, et al. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Carcinogenesis. 2000;21(8):1619–1622. doi: 10.1093/carcin/21.5.619.
  • Washington MK, Powell AE, Sullivan R, et al. Pathology of rodent models of intestinal cancer progress report and recommendations. Gastroenterology. 2013;144(4):705–717. doi: 10.1053/j.gastro.2013.01.067.
  • Seeni A, Takahashi S, Takeshita K, et al. Suppression of prostate cancer growth by resveratrol in the transgenic for adenocarcinoma of prostate (TRAP) model. Asian Pac J Cancer Prev. 2008;9(1):7–14.
  • Mohapatra P, Satapathy SR, Das D, et al. Resveratrol mediated cell death in cigarette smoke transformed breast epithelial cells is through induction of p21Waf1/Cip1 and inhibition of long patch base excision repair pathway. Toxicol Appl Pharmacol. 2014;275(3):221–231. doi: 10.1016/j.taap.2014.01.011.
  • Bhat KPL, Lantvit D, Christov K, et al. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res. 2001;61(20):7456–7463.
  • Kalra N, Roy P, Prasad S, et al. Resveratrol induces apoptosis involving mitochondrial pathways in mouse skin tumorigenesis. Life Sci. 2008;82(7–8):348–358. doi: 10.1016/j.lfs.2007.11.006.
  • Harikumar KB, Kunnumakkara AB, Sethi G, et al. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010;127(2):257–268. doi: 10.1002/ijc.25041.
  • Honari M, Shafabakhsh R, Reiter RJ, et al. Resveratrol is a promising agent for colorectal cancer prevention and treatment: focus on molecular mechanisms. Cancer Cell Int. 2019;19(1):1–8. doi: 10.1186/s12935-019-0906-y.
  • Kogure T, Kinghorn AD, Yan I, et al. Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer. PLoS One. 2013;8(9):e76136. doi: 10.1371/journal.pone.0076136.
  • Bordeleau M-E, Robert F, Gerard B, et al. Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model. J Clin Invest. 2008;118(7):1–10. doi: 10.1172/JCI34753.
  • Chen WL, Pan L, Kinghorn AD, et al. Silvestrol induces early autophagy and apoptosis in human melanoma cells. BMC Cancer. 2016;16(1):1–10. doi: 10.1186/s12885-015-1988-0.
  • Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678–5685. doi: 10.1158/1078-0432.CCR-04-2421.
  • Weaver BA. How taxol/paclitaxel kills cancer cells. MBoC. 2014;25(18):2677–2681. doi: 10.1091/mbc.e14-04-0916.
  • Tsunetoh S, Terai Y, Sasaki H, et al. Topotecan as a molecular targeting agent which blocks the Akt and VEGF cascade in platinum-resistant ovarian cancers. Cancer Biol Ther. 2010;10(11):1137–1146. doi: 10.4161/cbt.10.11.13443.
  • Olsen IH, Knigge U, Federspiel B, et al. Topotecan monotherapy in heavily pretreated patients with progressive advanced stage neuroendocrine carcinomas. J Cancer. 2014;5(8):628–632. doi: 10.7150/jca.9409.
  • Mainwaring PN, Nicolson MC, Hickish T, et al. Continuous infusional topotecan in advanced breast and non-small-cell lung cancer: no evidence of increased efficacy. Br J Cancer. 1997;76(12):1636–1639. doi: 10.1038/bjc.1997.609.
  • Almatar M, Makky E. Chemotherapeutic agents: taxol and vincristine isolated from endophytic fungi. Int J Curr Pharm Rev Res. 2015;6(1):56–88.
  • Starobova H, Vetter I. Pathophysiology of chemotherapy-induced peripheral neuropathy. Front Mol Neurosci. 2017;10(10):174. doi: 10.3389/fnmol.2017.00174.
  • Ren X, Zhao B, Chang H, et al. Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Mol Med Rep. 2018;17(6):8289–8299. doi: 10.3892/mmr.2018.8868.
  • Gallego-Jara J, Lozano-Terol G, Sola-Martínez RA, et al. A compressive review about Taxol®: history and future challenges. Molecules. 2020;25(24):5986. doi: 10.3390/molecules25245986.
  • Kampan NC, Madondo MT, McNally OM, et al. Paclitaxel and its evolving role in the management of ovarian cancer. Biomed Res Int. 2015;2015:1–21. doi: 10.1155/2015/413076.
  • Torres K, Horwitz SB. Mechanisms of taxol-induced cell death are concentration dependent. Cancer Res. 1998;58(16):3620–3626.
  • Mikuła J, Martyna AP, Paweł W, et al. B. Comprehensive review on how platinum and taxane based chemotherapy of ovarian cancer affects biology of normal cells. Cell Mol Life Sci. 2019;76(4):681–697. doi: 10.1007/s00018-018-2954-1.
  • Alam MM, Naeem M, Khan MMA, et al. Vincristine and vinblastine anticancer Catharanthus alkaloids : pharmacological applications and strategies for yield improvement. In: Naeem M, Aftab T, Khan M, editors. Catharanthus roseus. Cham: Springer; 2017. p. 277–307. doi: 10.1007/978-3-319-51620-2_11.
  • Molad Y. Update on colchicine and its mechanism of action. Curr Rheumatol Rep. 2002;4(3):252–256. doi: 10.1007/s11926-002-0073-2.
  • Hartung EF. History of the use of colchicum and related medicaments in gout: with suggestions for further research. Ann Rheum Dis. 1954;13(3):190–200. doi: 10.1136/ard.13.3.190.
  • Bhattacharyya B, Panda D, Gupta S, et al. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev. 2008;28(1):155–183. doi: 10.1002/med.20097.
  • Massarotti A, Coluccia A, Silvestri R, et al. The tubulin colchicine domain: a molecular modeling perspective. ChemMedChem. 2012;7(1):33–42. doi: 10.1002/cmdc.201100361.
  • Charpentier MS, Whipple RA, Vitolo MI, et al. Curcumin targets breast cancer stem–like cells with microtentacles that persist in mammospheres and promote reattachment. Cancer Res. 2014;74(4):1250–1260. doi: 10.1158/0008-5472.CAN-13-1778.
  • Meshki J, Douglas SD, Hu M, et al. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner. PLoS One. 2011;6(9):e25332. doi: 10.1371/journal.pone.0025332.
  • Ganguly A, Yang H, Zhang H, et al. Microtubule dynamics control tail retraction in migrating vascular endothelial cells. Mol Cancer Ther. 2013;12(12):2837–2846. doi: 10.1158/1535-7163.MCT-13-0401.
  • Kumar B, Kumar R, Skvortsova I, et al. Mechanisms of tubulin binding ligands to target cancer cells: updates on their therapeutic potential and clinical trials. CCDT. 2017;17(4):357–375. doi: 10.2174/1568009616666160928110818.
  • Parra-Medina R, Herrera S, Mejia J. Systematic review of microthrombi in COVID-19 autopsies. Acta Haematol. 2021;144(5):476–483. doi: 10.1159/000515104.
  • Schlesinger N, Firestein BL, Brunetti L. Colchicine in COVID-19: an old drug. Curr Pharmacol Rep. 2020;6(4):137–145. doi: 10.1007/s40495-020-00225-6.
  • Sandur SK, Pandey MK, Sung B, et al. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 2007;28(8):1765–1773. doi: 10.1093/carcin/bgm123.
  • Liu Y, Hong XQ. Effect of three different curcumin pigmens on the prdiferation of vascular smooth muscle cells by ox-LDL and the expression of LDL-R. China J Chin Materia Medica. 2006;31(6):500–503.
  • Kim DSHL, Park SY, Kim JY. Curcuminoids from Curcuma longa L.(zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from βA (1–42) insult. Neurosci Lett. 2001;303(1):57–61. doi: 10.1016/S0304-3940(01)01677-9.
  • Zhang D, Kanakkanthara A. Beyond the paclitaxel and vinca alkaloids: next generation of plant-derived microtubule-targeting agents with potential anticancer activity. Cancers. 2020;12(7):1721. doi: 10.3390/cancers12071721.
  • Mohamadian M, Bahrami A, Binabaj MM, et al. Molecular targets of curcumin and its therapeutic potential for ovarian cancer. Nutr Cancer. 2022;74(8):2713–2730. doi: 10.1080/01635581.2022.2049321.
  • Wang M, Jiang S, Zhou L, et al. Potential mechanisms of action of curcumin for cancer prevention: focus on cellular signaling pathways and miRNAs. Int J Biol Sci. 2019;15(6):1200–1214. doi: 10.7150/ijbs.33710.
  • Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):e2900.
  • Anand P, Kunnumakkara AB, Newman RA, et al. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–818. doi: 10.1021/mp700113r.
  • Shehzad A, Khan S, Shehzad O, et al. Curcumin therapeutic promises and bioavailability in colorectal cancer. Drugs Today. 2010;46(7):523.
  • Jaxel C, Kohn KW, Wani MC, et al. Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res. 1989;49(6):1465–1469.
  • Sinha BK. Topoisomerase inhibitors. Drugs. 1995;49(1):11–19. A review of their therapeutic potential in cancer. doi: 10.2165/00003495-199549010-00002.
  • Gupta M, Fujimori A, Pommier Y. Eukaryotic DNA topoisomerases I. Biochim Biophys Acta (BBA)-Gene Struct Expr. 1995;1262(1):1–14. doi: 10.1016/0167-4781(95)00029-G.
  • Pommier Y. Eukaryotic DNA topoisomerase I: genome gatekeeper and its intruders, camptothecins. Semin Oncol. 1996;23(1):3–10.
  • Giovanella BC, Stehlin JS, Wall ME, et al. DNA topoisomerase I–targeted chemotherapy of human colon cancer in xenografts. Science. 1989;246(4933):1046–1048. doi: 10.1126/science.2555920.
  • Xu Y, Villalona-Calero MA. Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol. 2002;13(12):1841–1851. doi: 10.1093/annonc/mdf337.
  • Kamal A, Hussaini SM, Malik MS. Recent developments towards podophyllotoxin congeners as potential apoptosis inducers. ACAMC. 2015;15(5):565–574. doi: 10.2174/1871520614666141130125623.
  • Kuhn M, Keller-Juslén C, Von Wartburg A. Partialsynthese von 4′-demethylepipodophyllotoxin. 22. Mitteilung über mitosehemmende naturstoffe. Helv Chim Acta. 1969;52(4):944–947. doi: 10.1002/hlca.19690520410.
  • Holthuis JJ. Etoposide and teniposide, bioanalysis, metabolism and clinical pharmacokinetics. Pharm Weekbl Sci. 1988;10(3):101–116. doi: 10.1007/BF01959294.
  • Yalowich JC, Goldman ID. Analysis of the inhibitory effects of VP-16-213 (etoposide) and podophyllotoxin on thymidine transport and metabolism in Ehrlich ascites tumor cells in vitro. Cancer Res. 1984;44(3):984–989.
  • Loike JD, Horwitz SB. Effect of VP-16-213 on the intracellular degradation of DNA in HeLa cells. Biochemistry. 1976;15(25):5443–5448. doi: 10.1021/bi00670a004.
  • Loike JD, Brewer CF, Sternlicht H, et al. Structure-activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. Cancer Res. 1978;38(9):2688–2693.
  • Loike JD, Horwitz SB. Effects of podophyllotoxin and VP-16-213 on microtubule assembly in vitro and nucleoside transport in HeLa cells. Biochemistry. 1976;15(25):5435–5443. doi: 10.1021/bi00670a003.
  • Rowe T, Kupfer G, Ross W. Inhibition of epipodophyllotoxin cytotoxicity by interference with topoisomerase-mediated DNA cleavage. Biochem Pharmacol. 1985;34(14):2483–2487. doi: 10.1016/0006-2952(85)90530-1.
  • Verdaguer E, Jiménez A, Canudas AM, et al. Inhibition of cell cycle pathway by flavopiridol promotes survival of cerebellar granule cells after an excitotoxic treatment. J Pharmacol Exp Ther. 2004;308(2):609–616. doi: 10.1124/jpet.103.057497.
  • Srikumar T, Padmanabhan J. Potential use of flavopiridol in treatment of chronic diseases. Adv Exp Med Biol. 2016;929:209–228. doi: 10.1007/978-3-319-41342-6_9.
  • Cencic R, Carrier M, Galicia-Vázquez G, et al. Activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol. PLoS One. 2009;4(4):e5223. doi: 10.1371/journal.pone.0005223.
  • Ashrafizadeh M, Bakhoda MR, Bahmanpour Z, et al. Apigenin as tumor suppressor in cancers: biotherapeutic activity, nanodelivery, and mechanisms with emphasis on pancreatic cancer. Front Chem. 2020;8(8):829. doi: 10.3389/fchem.2020.00829.
  • Yan X, Qi M, Li P, et al. Apigenin in cancer therapy : anti‑cancer effects and mechanisms of action. Cell Biosci. 2017;7(1):1–16. doi: 10.1186/s13578-017-0179-x.
  • Wang X, Yang Y, An Y, et al. The mechanism of anticancer action and potential clinical use of kaempferol in the treatment of breast cancer. Biomed Pharmacother. 2019;117:109086. doi: 10.1016/j.biopha.2019.109086.
  • Stiborová M, Poljaková J, Martínková E, et al. Ellipticine cytotoxicity to cancer cell lines - a comparative study. Interdiscip Toxicol. 2011;4(2):98–105. doi: 10.2478/v10102-011-0017-7.
  • Karthikeyan S, Leung T, Ladias JA. Structural basis of the Na+/H + exchanger regulatory factor PDZ1 interaction with the carboxyl-terminal region of the cystic fibrosis transmembrane conductance regulator. J Biol Chem. 2001;276(23):19683–19686. doi: 10.1074/jbc.C100154200.
  • Rauf A, Imran M, Butt MS, et al. Resveratrol as an anti-cancer agent a review. Crit Rev Food Sci Nutr. 2018;58(9):1428–1447. doi: 10.1080/10408398.2016.1263597.
  • Cichewicz RH, Kouzi A. Chemistry biological activity and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med Res Rev. 2004;24(1):90–114. doi: 10.1002/med.10053.
  • Pisha E, Chai H, Lee I-S, et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med. 1995;1(10):1046–1051. doi: 10.1038/nm1095-1046.
  • Fulda S, Friesen C, Los M, et al. Betulinic acid triggers CD95 (APO-1/fas)-and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res. 1997;57(21):4956–4964.
  • Thurnher D, Turhani D, Pelzmann M, et al. Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck J Sci Spec Head Neck. 2003;25(9):732–740. doi: 10.1002/hed.10231.
  • Zuco V, Supino R, Righetti SC, et al. Selective cytotoxicity of betulinic acid on tumor cell lines but not on normal cells. Cancer Lett. 2002;175(1):17–25. doi: 10.1016/S0304-3835(01)00718-2.
  • Selzer E, Pimentel E, Wacheck V, et al. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells. J Invest Dermatol. 2000;114(5):935–940. doi: 10.1046/j.1523-1747.2000.00972.x.
  • Fulda S, Debatin KM. Sensitization for anticancer drug-induced apoptosis by betulinic acid. Neoplasia. 2005;7(2):162–170. doi: 10.1593/neo.04442.
  • Fulda S, Jeremias I, Debatin KM. Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells. Oncogene. 2004;23(46):7611–7620. doi: 10.1038/sj.onc.1207970.
  • Liu H, Zhang H, Han Y, et al. Bacterial extracellular vesicles-based therapeutic strategies for bone and soft tissue tumors therapy. Theranostics. 2022;12(15):6576–6594. doi: 10.7150/thno.78034.
  • Wang J, Li X, Wang S, et al. Bone-targeted exosomes: strategies and applications. Adv Healthc Mater. 2023;12(18):e2203361. doi: 10.1002/adhm.202203361.
  • Huang B, Yin Z, Zhou F, et al. Functional anti-bone tumor biomaterial scaffold: construction and application. J Mater Chem B. 2023;11(36):8565–8585. doi: 10.1039/D3TB00925D.
  • Huang X, Guo H, Wang L, et al. Engineered microorganism-based delivery systems for targeted cancer therapy a narrative review. Biomater Transl. 2022;3(3):201–212. doi: 10.12336/biomatertransl.2022.03.004.
  • Watt SM. The long and winding road, homeostatic and disordered haematopoietic microenvironmental niches a narrative review. Biomater Transl. 2022;28:3(1):31–54. doi: 10.12336/biomatertransl.2022.01.005.

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