Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells

Molecular Medicine Reports

Volumn 11, Issue 4, 2015, Pages 3094-3100

  Sun, Li ^a   Peng, Qisong ^b   Qu, Lili ^a   Gong, Lailing ^a   Si, Jin ^a  

^a THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^b THE AFFILIATED JIANGNING HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

Author keywords

Apoptosis; Fas; Hepatocellular carcinoma; Icaritin; Mitochondrial pathway

Indexed keywords

ANTINEOPLASTIC AGENT; CASPASE; CASPASE 8; FAS LIGAND; ICARITIN; PROTEIN BAX; PROTEIN BCL 2; UNCLASSIFIED DRUG; CASPASE 3; FLAVONOID;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL LINE; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; FLOW CYTOMETRY; GENE EXPRESSION; GROWTH INHIBITION; HEPATOCELLULAR CARCINOMA CELL LINE; HEPATOMA CELL; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; MITOCHONDRION; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SMMC 7721 CELL LINE; WESTERN BLOTTING; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; LIVER NEOPLASMS; METABOLISM; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

EPIMEDIUM;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; CARCINOMA, HEPATOCELLULAR; CASPASE 3; CASPASES; CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; FLAVONOIDS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LIVER NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84921358091     PISSN: 17912997     EISSN: 17913004     Source Type: Journal    
DOI: 10.3892/mmr.2014.3007     Document Type: Article

References (40)

1. McKillop IH, Moran DM, Jin X and Koniaris LG: Molecular pathogenesis of hepatocellular carcinoma. J Surg Res 136: 125-135, 2006.
2. Bruix J, Boix L, Sala M and Llovet JM: Focus on hepatocellular carcinoma. Cancer Cell 5: 215-219, 2004.
3. Trevisani F, Cantarini MC, Wands JR and Bernardi M: Recent advances in the natural history of hepatocellular carcinoma. Carcinogenesis 29: 1299-1305, 2008.
4. Kusakabe A, Tanaka Y, Orito E, et al: A weak association between occult HBV infection and non-B non-c hepatocellular carcinoma in Japan. J Gastroenterol 42: 298-305, 2007.
5. El-Serag HB, Siegel AB, Davila JA, Shaib YH, Cayton-Woody M, McBride R and McGlynn KA: Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: a population-based study. J Hepatol 44 158-166, 2006.
6. Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet 362: 1907-1917, 2003.
7. Plataniotis G and Castiglione M; ESMO Guidelines Working Group: Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2: v41-v45, 2010.
8. Gehrig PA and Bae-Jump VL: Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 116: 187-194, 2010.
9. Middleton E Jr, Kandaswami C and Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52: 673-751, 2000.
10. Li YL, Gan GP, Zhang HZ, Wu HZ, Li CL, Huang YP, Liu YW and Liu JW: A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines J Ethnopharmacol 113: 115-124, 2007
11. Díaz JG, Carmona AJ, Torres F, Quintana J, Estévez F and Herz W: Cytotoxic activities of flavonoid glycoside acetates from Consolida oliveriana. Planta Med 74: 171-174, 2008.
12. Wang Z, Wang H, Wu J, Zhu D, Zhang X, Ou L, Yu Y and Lou Y: Enhanced co-expression of beta-tubulin III and choline acetyltransferase in neurons from mouse embryonic stem cells promoted by icaritin in an estrogen receptor-independent manner. Chem Biol Interact 179: 375-385, 2009.
13. Wo YB, Zhu DY, Hu Y, Wang ZQ, Liu J and Lou YJ: Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells. J Cell Biochem 103: 1536-1550, 2008.
14. Zhang G, Qin L, Sheng H, Wang XL, Wang YX, Yeung DK, Griffith JF, Yao XS, Xie XH, Li ZR, Lee KM and Leung KS: A novel semisynthesized small molecule icaritin reduces incidence of steroid-associated osteonecrosis with inhibition of both thrombosis and lipid-deposition in a dose-dependent manner. Bone 44: 345-356, 2009.
15. Huang X, Zhu D and Lou Y: A novel anticancer agent, icaritin, induced cell growth inhibition, Gl arrest and mitochondrial transmenbrane potential drop in human prostate carcinoma PC-3 cells. Eur J Pharmacol 564: 26-36, 2007.
16. Wang ZQ and Lou YJ: Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells. Eur J Pharmacol 504: 147-153, 2004.
17. Guo Y, Zhang X, Meng J and Wang ZY: An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol 658: 114-122, 2011.
18. Tong JS, Zhang QH, Huang X, Fu XQ, Qi ST, Wang Y P, Hou Y, Sheng J and Sun QY: Icaritin causes sustained ERK1/2 activation and induces apoptosis in human endometrial cancer cells. PLoS One 6: e16781, 2011.
19. Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 55: 74-108, 2005.
20. Zhou NN, Tang J, Chen WD, Feng GK, Xie BF, Liu ZC, Yang D and Zhu XF: Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells. Life Sci 90: 770-775, 2012.
21. Wang CZ, Calway T and Yuan CS: Herbal medicines as adjuvants for cancer therapeutics. Am J Chin Med 40: 657-669, 2012.
22. Ben-Arye E, Schiff E, Hassan E, Mutafoglu K, Lev-Ari S, Steiner M, Lavie O, Polliack A, Silbermann M and Lev E: Integrative oncology in the Middle East: from traditional herbal knowledge to contemporary cancer care. Ann Oncol 23: 211-221, 2012.
23. Li J, Liu P, Zhang R, Cao L, Qian H, Liao J, Xu W, Wu M and Yin Z: Icaritin induces cell death in activated hepatic stellate cells through mitochondrial activated apoptosis and ameliorates the development of liver fibrosis in rats. J Ethnopharmacol 137: 714-723, 2011.
24. Zhou J, Wu J, Chen X, Fortenbery N, Eksioglu E, Kodumudi KN, Pk EB, Dong J, Djeu JY and Wei S: Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions. Int Immunopharmacol 11: 890-898, 2011.
25. Huang J, Yuan L, Wang X, Zhang TL and Wang K: Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci 81: 832-840, 2007.
26. He J, Wang Y, Duan F, Jiang H, Chen MF and Tang SY: Icaritin induces apoptosis of HepG2 cells via the JNK1 signaling pathway independent of the estrogen receptor. Planta Med 76: 1834-1839, 2010.
27. Golbano JM, Lóppez-Aparicio P, Recio MN and Pérez-Albarsanz MA: Finasteride induces apoptosis via Bcl-2, Bcl-xL, Bax and caspase-3 proteins in LNCaP human prostate cancer cell line. Int J Oncol 32: 919-924, 2008.
28. Kroemer G and Reed JC: Mitochondrial control of cell death. Nat Med 6: 513-519, 2000.
29. van Loo G, Saelens X, van Gurp M, MacFarlane M, Martin SJ and Vandenabeele P: The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet. Cell Death Differ 9: 1031-1042, 2002.
30. Llambi F, Moldoveanu T, Tait SW, Bouchier-Hayes L, Temirov J, McCormick LL, Dillon CP and Green DR: A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol Cell 44: 517-531, 2011.
31. Wang X: The expanding role of mitochondria in apoptosis. Genes Dev 15: 2922-2933, 2001.
32. Susnow N, Zeng L, Margineantu D and Hockenbery DM: Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 19: 42-49, 2009.
33. Tait SW and Green DR: Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11: 621-632, 2010.
34. Fulda S and Debatin KM: Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811, 2006.
35. Yamaguchi Y, Shiraki K, Fuke H, Inoue T, Miyashita K, Yamanaka Y and Nakano T: Adenovirus-mediated transfection of caspase-8 sensitizes hepatocellular carcinoma to TRAIL- and chemotherapeutic agent-induced cell death. Biochim Biophys Acta 1763: 844-853, 2006.
36. Wang SH, Chen LM, Yang WK and Lee JD: Increased extrinsic apoptotic pathway activity in patients with hepatocellular carcinoma following transarterial embolization. World J Gastroenterol 17: 4675-4681, 2011.
37. Muppidi JR and Siegel RM: Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death. Nat Immunol 5: 182-189, 2004.
38. Abd El-Ghany RM, Sharaf NM, Kassem LA, Mahran LG and Heikal OA: Thymoquinone triggers anti-apoptotic signaling targeting death ligand and apoptotic regulators in a model of hepatic ischemia reperfusion injury. Drug Discov Ther 3: 296-306, 2009.
39. Hyer ML, Shi R, Krajewska M, Meyer C, Lebedeva IV, Fisher PB and Reed JC: Apoptotic activity and mechanism of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic-acid and related synthetic triterpenoids in prostate cancer. Cancer Res 68: 2927-2933, 2008.
40. Zhang L, Zhang Y, Zhang L, Yang X and Lv Z: Lupeol, a dietary triterpene, inhibited growth, and induced apoptosis through down-regulation of DR3 in SMMC7721 cells. Cancer Invest 27: 163-170, 2009.