Schisandra chinensis Bee Pollen Extract Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells via Ferroptosis-, Wnt-, and Focal Adhesion–Signaling Pathways

References

• Zhao M. Hepatic arterial infusion chemotherapy in the era of precise medicine. J Sun Yat-Sen Univ Med Sci. 2019;5(5):648–656.
   Google Scholar
• Cao M, Li H, Sun D, et al. Global epidemiology of liver cancer in 2020. Chin J Cancer. 2022;29(5):322–328. doi:10.16073/j.cnki.cjcpt.2022.05.03
   Google Scholar
• Qi L, Luo Q, Zhang Y, et al. Advances in toxicological research of the anticancer drug cisplatin. Chem Res Toxicol. 2019;32(8):1469–1486. doi:10.1021/acs.chemrestox.9b00204
   PubMed Web of Science ®Google Scholar
• Yang K, Wu D, Ye X, et al. Characterization of chemical composition of bee pollen in China. J Agric Food Chem. 2013;61(3):708–718. doi:10.1021/jf304056b
   PubMed Web of Science ®Google Scholar
• Han S, Chen L, Zhang Y, et al. Lotus bee pollen extract inhibits isoproterenol-induced hypertrophy via JAK2/STAT3 signaling pathway in rat H9c2 cells. Antioxidants. 2023;12(1):88. doi:10.3390/antiox12010088
   Web of Science ®Google Scholar
• Li QQ, Wang K, Marcucci MC, et al. Nutrient-rich bee pollen: a treasure trove of active natural metabolites. J Funct Foods. 2018;49:472–484. doi:10.1016/j.jff.2018.09.008
   Web of Science ®Google Scholar
• Shi P, Geng Q, Chen L, et al. Schisandra chinensis bee pollen’s chemical profiles and protective effect against H2O2-induced apoptosis in H9c2 cardiomyocytes. BMC Compl Med Ther. 2020;20(1):274. doi:10.1186/s12906-020-03069-1
   PubMedGoogle Scholar
• Denisow B, Denisow-Pietrzyk M. Biological and therapeutic properties of bee pollen: a review. J Sci Food Agric. 2016;96(13):4303–4309. doi:10.1002/jsfa.7729
   PubMed Web of Science ®Google Scholar
• Huang H, Shen Z, Geng Q, et al. Protective effect of Schisandra chinensis bee pollen extract on liver and kidney injury induced by cisplatin in rats. Biomed Pharmacother. 2017;95:1765–1776. doi:10.1016/j.biopha.2017.09.083
   PubMed Web of Science ®Google Scholar
• Sun L, Guo Y, Zhang Y, et al. Antioxidant and anti-tyrosinase activities of phenolic extracts from rape bee pollen and inhibitory melanogenesis by cAMP/MITF/TYR pathway in B16 mouse melanoma cells. Front Pharmacol. 2017;8:104. doi:10.3389/fphar.2017.00104
   PubMed Web of Science ®Google Scholar
• Katz L, Baltz RH. Natural product discovery: past, present, and future. J Ind Microbiol. 2016;43:155–176. doi:10.1007/s10295-015-1723-5
   Google Scholar
• Omar WAW, Azhar NA, Fadzilah NH, et al. Bee pollen extract of Malaysian stingless bee enhances the effect of cisplatin on breast cancer cell lines. Asian Pac J Trop Biomed. 2016;6(3):265–269. doi:10.1016/j.apjtb.2015.12.011
   Web of Science ®Google Scholar
• Al-Yousef HM, Amina M, Alqahtani AS, et al. Pollen bee aqueous extract-based synthesis of silver nanoparticles and evaluation of their anti-cancer and anti-bacterial activities. Processes. 2020;8:524. doi:10.3390/pr8050524
   Web of Science ®Google Scholar
• Saisavoey T, Sangtanoo P, Srimongkol P, et al. Hydrolysates from bee pollen could induced apoptosis in human bronchogenic carcinoma cells (ChaGo-K-1). J Food Sci Technol. 2021;58(2):752–763. doi:10.1007/s13197-020-04592-2
   PubMed Web of Science ®Google Scholar
• Tuoheti T, Rasheed HA, Meng L, et al. High hydrostatic pressure enhances the anti-proliferative properties of lotus bee pollen on the human prostate cancer PC-3 cells via increased metabolites. J Ethnopharmacol. 2020;261:113057. doi:10.1016/j.jep.2020.113057
   PubMed Web of Science ®Google Scholar
• Wu YD, Lou YJ. A steroid fraction of chloroform extract from bee pollen of Brassica campestris induces apoptosis in human prostate cancer PC-3 cells. Phytother Res. 2007;21(11):1087–1091. doi:10.1002/ptr.2235
   PubMed Web of Science ®Google Scholar
• Wang B, Diao Q, Zhang Z, et al. Antitumor activity of bee pollen polysaccharides from Rosa rugosa. Mol Med Rep. 2013;7(5):1555–1558. doi:10.3892/mmr.2013.1382
   PubMed Web of Science ®Google Scholar
• Uçar M, Deger O, Gerigelmez AY, et al. Effect of Turkish pollen and propolis extracts on caspase-3 activity in myeloid cancer cell lines. Trop J Pharm Res. 2016;15(11):2445–2449. doi:10.4314/tjpr.v15i11.20
   Web of Science ®Google Scholar
• Choi SK, Lee YG, Wang RB, et al. Dibenzocyclooctadiene lignans from the fruits of Schisandra chinensis and their cytotoxicity on human cancer cell lines. Appl Biol Chem. 2020;63:39. doi:10.1186/s13765-020-00524-y
   Web of Science ®Google Scholar
• Ji M, Fu B, Zhang Y. Recent progress of analytical methods of proteomics based on mass spectrometry. J Chin Mass Spectrom Soc. 2021;42(5):862–877. doi:10.7538/zpxb.2021.0091
   Google Scholar
• Zhang Y, Cai Q, Luo Y, et al. Integrated top-down and bottom-up proteomics mass spectrometry for the characterization of endogenous ribosomal protein heterogeneity. J Pharm Anal. 2023;13(1):63–72. doi:10.1016/j.jpha.2022.11.003
   PubMed Web of Science ®Google Scholar
• Li S, Liu H, Lin Z, et al. Isoorientin attenuates doxorubicin-induced cardiac injury via the activation of MAPK, Akt, and Caspase-dependent signaling pathways. Phytomed. 2022;101:154105. doi:10.1016/j.phymed.2022.154105
   PubMed Web of Science ®Google Scholar
• Meng Y, Chen J, Liu Y, et al. A highly efficient protein Corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers. J Pharm Anal. 2022;12(6):879–888. doi:10.1016/j.jpha.2022.07.002
   PubMed Web of Science ®Google Scholar
• Shi P, Du T, Meng F, et al. Ethanol extract of propolis alleviates diabetic cardiomyopathy via JAK2/STAT3 signaling pathway. J Funct Foods. 2023;107:105688. doi:10.1016/j.jff.2023.105688
   Web of Science ®Google Scholar
• Yang Y, Liu M, Li H, et al. Proteomics analysis of the protective effect of canola (Brassica campestris L.) bee pollen flavonoids on the tert-butyl hydroperoxide-induced EA.hy926 cell injury model. J Funct Foods. 2020;75:104223. doi:10.1016/j.jff.2020.104223
   Web of Science ®Google Scholar
• Zhao L, Pan F, Zhou N, et al. Quantitative proteomics and bioinformatics analyses reveal the protective effects of cyanidin-3-O-glucoside and its metabolite protocatechuic acid against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced cytotoxicity in HepG2 cells via apoptosis-related pathways. Food Chem Toxicol. 2021;153:112256. doi:10.1016/j.fct.2021.112256
   PubMed Web of Science ®Google Scholar
• Tang H, Liu X, Wang R, et al. Effects of oleanolic acid and chlorogenic acid on HepG2 cells and P450 enzyme expression. Chin Tradit Pat Med. 2013;35:2576–2580.
   Google Scholar
• Wu LF, Ye YQ, Huang GY, et al. Involvement of endoplasmic reticulum stress in adenosine-induced human hepatoma HepG2 cell apoptosis. Oncol Rep. 2011;26(1):73–79. doi:10.3892/or.2011.1247
   PubMed Web of Science ®Google Scholar
• Ma RH, Ni ZJ, Thakur K, et al. Transcriptome and proteomics conjoint analysis reveal metastasis inhibitory effect of 6-shogaol as ferroptosis activator through the PI3K/AKT pathway in human endometrial carcinoma in vitro and in vivo. Food Chem Toxicol. 2022;170:113499. doi:10.1016/j.fct.2022.113499
   PubMed Web of Science ®Google Scholar
• Ryter SW, Tyrrell RM. The heme synthesis and degradation pathways: role in oxidant sensitivity, Heme oxygenase has both pro- and antioxidant properties. Free Radic Biol Med. 2000;28(2):289–309. doi:10.1016/s0891-5849(99)00223-3
   PubMed Web of Science ®Google Scholar
• Chang LC, Chiang SK, Chen SE, et al. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis. Cancer Lett. 2018;416:124–137. doi:10.1016/j.canlet.2017.12.025
   PubMed Web of Science ®Google Scholar
• Zhu X, Huang S, Zeng L, et al. HMOX-1 inhibits TGF-β-induced epithelial-mesenchymal transition in the MCF-7 breast cancer cell line. Int J Mol Med. 2017;40(2):411–417. doi:10.3892/ijmm.2017.3027
   PubMed Web of Science ®Google Scholar
• Gueron G, De Siervi A, Ferrando M, et al. Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells. Mol Cancer Res. 2009;7(11):1745–1755. doi:10.1158/1541-7786.MCR-08-0325
   PubMed Web of Science ®Google Scholar
• Fan H, Ai R, Mu S, et al. MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2. Bioengineered. 2022;13(5):12021–12029. doi:10.1080/21655979.2022.2054194
   PubMed Web of Science ®Google Scholar
• Ebrahimi KH, Hagedoorn P-L, Hagen WR. Unity in the biochemistry of the iron-storage proteins ferritin and bacterioferritin. Chem Rev. 2015;115(1):295–326. doi:10.1021/cr5004908
   PubMed Web of Science ®Google Scholar
• Shi Y, He B, You L, et al. Roles of secreted frizzled-related proteins in cancer. Acta Pharmacol Sin. 2007;28(9):1499–1504. doi:10.1111/j.1745-7254.2007.00692.x
   PubMed Web of Science ®Google Scholar
• Yan J, Liu T, Zhou X, et al. FZD6, targeted by miR-21, represses gastric cancer cell proliferation and migration via activating non-canonical wnt pathway. Am J Transl Res. 2016;8(5):2354–2364.
   PubMed Web of Science ®Google Scholar
• Yang J, Ye Z, Mei D, et al. Long noncoding RNA DLX6-AS1 promotes tumorigenesis by modulating miR-497-5p/FZD4/FZD6/Wnt/β-catenin pathway in pancreatic cancer. Cancer Manage Res. 2019;11:4209–4221. doi:10.2147/CMAR.S194453
   PubMed Web of Science ®Google Scholar
• Montalto FI, De Amicis F. Cyclin D1 in cancer: a molecular connection for cell cycle control, adhesion and invasion in tumor and stroma. Cells. 2020;9(12):2648. doi:10.3390/cells9122648
   PubMed Web of Science ®Google Scholar
• Wu SY, Lan SH, Liu HS. Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis. Autophagy. 2019;15(4):729–730. doi:10.1080/15548627.2019.1569918
   PubMed Web of Science ®Google Scholar
• Ding H, Wang Y, Zhang H. CCND1 silencing suppresses liver cancer stem cell differentiation and overcomes 5-Fluorouracil resistance in hepatocellular carcinoma. J Pharmacol Sci. 2020;143(3):219–225. doi:10.1016/j.jphs.2020.04.006
   PubMed Web of Science ®Google Scholar
• Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene. 2010;29(36):4989–5005. doi:10.1038/onc.2010.236
   PubMed Web of Science ®Google Scholar
• Parsons JT, Slack-Davis J, Tilghman R, et al. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res. 2008;14(3):627–632. doi:10.1158/1078-0432.CCR-07-2220
   PubMed Web of Science ®Google Scholar
• Moreno-Layseca P, Icha J, Hamidi H, et al. Integrin trafficking in cells and tissues. Nat Cell Biol. 2019;21(2):122–132. doi:10.1038/s41556-018-0223-z
   PubMed Web of Science ®Google Scholar
• Liu X, Tian H, Li H, et al. Derivate isocorydine (d-ICD) suppresses migration and invasion of hepatocellular carcinoma cell by downregulating ITGA1 expression. Int J Mol Sci. 2017;18(3):514. doi:10.3390/ijms18030514
   PubMed Web of Science ®Google Scholar
• Wan J, Wen D, Dong L, et al. Establishment of monoclonal HCC cell lines with organ site-specific tropisms. BMC Cancer. 2015;15:678. doi:10.1186/s12885-015-1692-0
   PubMed Web of Science ®Google Scholar
• Kang CL, Qi B, Cai QQ, et al. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics. 2019;9(15):4421–4436. doi:10.7150/thno.32854
   PubMed Web of Science ®Google Scholar
• Yoshioka T, Otero J, Chen Y, et al. β4 Integrin signaling induces expansion of prostate tumor progenitors. J Clin Invest. 2013;123(2):682–699. doi:10.1172/JCI60720
   PubMed Web of Science ®Google Scholar
• Moilanen JM, Löffek S, Kokkonen N, et al. Significant role of collagen XVII and integrin β4 in migration and invasion of the less aggressive squamous cell carcinoma cells. Sci Rep. 2017;7:45057. doi:10.1038/srep45057
   PubMed Web of Science ®Google Scholar
• Hecker TP, Gladson CL. Focal adhesion kinase in cancer. Front Biosci. 2003;8:s705–714. doi:10.2741/1115
   PubMed Web of Science ®Google Scholar
• Siesser PMF, Hanks SK. The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res. 2006;12(11):3233–3237. doi:10.1158/1078-0432.CCR-06-0456
   PubMed Web of Science ®Google Scholar
• Zhou Y, Fukuda T, Hang Q, et al. Inhibition of fucosylation by 2-fluorofucose suppresses human liver cancer HepG2 cell proliferation and migration as well as tumor formation. Sci Rep. 2017;7(1):11563. doi:10.1038/s41598-017-11911-9
   PubMedGoogle Scholar
• Onodera K, Sakurada A, Notsuda H, et al. Growth inhibition of KRAS‑ and EGFR‑mutant lung adenocarcinoma by cosuppression of STAT3 and the SRC/ARHGAP35 axis. Oncol Rep. 2018;40(3):1761–1768. doi:10.3892/or.2018.6536
   PubMed Web of Science ®Google Scholar
• Wang D, Dou K, Xiang H, et al. Involvement of RhoA in progression of human hepatocellular carcinoma. J Gastroe Hepatol. 2007;22(11):1916–1920. doi:10.1111/j.1440-1746.2006.04534.x
   PubMed Web of Science ®Google Scholar
• Wang T, Rao D, Yu C, et al. RHO GTPase family in hepatocellular carcinoma. Exp Hematol Oncol. 2022;11(1):91. doi:10.1186/s40164-022-00344-4
   PubMed Web of Science ®Google Scholar
• Colón-Bolea P, García-Gómez R, Casar B. RAC1 Activation as a potential therapeutic option in metastatic cutaneous melanoma. Biomolecules. 2021;11(11):1554. doi:10.3390/biom11111554
   PubMed Web of Science ®Google Scholar
• Liu S, Yu M, He Y, et al. Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology. 2008;47(6):1964–1973. doi:10.1002/hep.22240
   PubMed Web of Science ®Google Scholar
• Chen H, Li Q, Yi R, et al. CircRNA casein kinase 1 gamma 1 (circ-CSNK1G1) plays carcinogenic effects in thyroid cancer by acting as miR-149-5p sponge and relieving the suppression of miR-149-5p on mitogen-activated protein kinase 1 (MAPK1). J Clin Lab Anal. 2022;36(2):e24188. doi:10.1002/jcla.24188
   PubMed Web of Science ®Google Scholar
• Zheng Y, Zhou C, Yu XX, et al. Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of β-Catenin. Cell Death Dis. 2018;9(2):179. doi:10.1038/s41419-017-0226-x
   PubMedGoogle Scholar
• Goult BT, Gingras AR, Bate N, et al. The domain structure of talin: residues 1815-1973 form a five-helix bundle containing a cryptic vinculin-binding site. FEBS Lett. 2010;584(11):2237–2241. doi:10.1016/j.febslet.2010.04.028
   PubMed Web of Science ®Google Scholar
• Ibrahim ESH, Naguib H, Emara DM, et al. Assessment of serum Talin-1 in liver cirrhosis and hepatocellular carcinoma. Egypt Liver J. 2022;12:19. doi:10.1186/s43066-022-00184-1
   Google Scholar
• Kanamori H, Kawakami T, Effendi K, et al. Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma. Oncology. 2011;80(5):406–415. doi:10.1159/000330734
   PubMed Web of Science ®Google Scholar
• Huang AH, Pan SH, Chang WH, et al. PARVA promotes metastasis by modulating ILK signalling pathway in lung adenocarcinoma. PLoS One. 2015;10(3):e0118530. doi:10.1371/journal.pone.0118530
   PubMed Web of Science ®Google Scholar
• Radeva MY, Kugelmann D, Spindler V, et al. PKA compartmentalization via AKAP220 and AKAP12 contributes to endothelial barrier regulation. PLoS One. 2014;9(9):e106733. doi:10.1371/journal.pone.0106733
   PubMed Web of Science ®Google Scholar
• Gelman IH. Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12. Cancer Metastasis Rev. 2012;31(3):493–500. doi:10.1007/s10555-012-9360-1
   PubMed Web of Science ®Google Scholar
• Yoon D-K, Jeong C-H, O JH, et al. AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity. Cancer Lett. 2007;254(1):111–118. doi:10.1016/j.canlet.2007.02.017
   PubMed Web of Science ®Google Scholar
• Han S, Wang L, Sun L, et al. MicroRNA-1251-5p promotes tumor growth and metastasis of hepatocellular carcinoma by targeting AKAP12. Biomed Pharmacother. 2020;122:109754. doi:10.1016/j.biopha.2019.109754
   PubMed Web of Science ®Google Scholar
• Fu J, Wang X, Yue Q. Functional loss of TAGLN inhibits tumor growth and increases chemosensitivity of non-small cell lung cancer. Biochem Biophys Res Com. 2020;529(4):1086–1093. doi:10.1016/j.bbrc.2020.06.066
   PubMed Web of Science ®Google Scholar
• Yu B, Chen X, Li J, et al. Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression. BMC Cell Biol. 2013;14:17. doi:10.1186/1471-2121-14-17
   PubMedGoogle Scholar
• Tatsukawa H, Hitomi K. Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis. Cells. 2021;10(7):1842. doi:10.3390/cells10071842
   PubMed Web of Science ®Google Scholar
• Yamaguchi H, Kuroda K, Sugitani M, et al. Transglutaminase 2 is upregulated in primary hepatocellular carcinoma with early recurrence as determined by proteomic profiles. Int J Oncol. 2017;50(5):749–1759. doi:10.3892/ijo.2017.3917
   Web of Science ®Google Scholar
• Yang P, Yu D, Zhou J, et al. TGM2 interference regulates the angiogenesis and apoptosis of colorectal cancer via Wnt/β-catenin pathway. Cell Cycle. 2019;18(10):1122–1134. doi:10.1080/15384101.2019.1609831
   PubMed Web of Science ®Google Scholar