Myricetin induces apoptosis in HepG2 cells through Akt/p70s6K/Bad signaling and mitochondrial apoptotic pathway

Anti-Cancer Agents in Medicinal Chemistry

Volumn 13, Issue 10, 2013, Pages 1575-1581

  Zhang, Xiao Hong ^a   Chen, Shi Yong ^a   Tang, Lin ^b   Shen, Ying Zhuo ^a   Luo, Lin ^a   Xu, Chen Wei ^a   Liu, Qiong ^a   Li, Duo ^c  

^a NINGBO UNIVERSITY   (China)

^b ZHEJIANG PHARMACEUTICAL COLLEGE   (China)

^c ZHEJIANG UNIVERSITY   (China)

Author keywords

Akt p70s6k1 bad signaling; Apoptosis; HepG2 cell; Mechanism; Myricetin

Indexed keywords

4 [5 (4 METHYL 1 PIPERAZINYL)[2,5' BI 1H BENZIMIDAZOL] 2' YL]PHENOL; CASPASE 3; CYTOCHROME C; FLUORESCEIN ISOTHIOCYANATE; LIPOCORTIN 5; MYRICETIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN BAD; PROTEIN BCL 2; PROTEIN KINASE B; S6 KINASE;

APOPTOSIS; ARTICLE; CELL CULTURE; CELL FRACTIONATION; CONTROLLED STUDY; DOWN REGULATION; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; HEPG2 CELL LINE; HUMAN; HUMAN CELL; MITOCHONDRIAL MEMBRANE POTENTIAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; STAINING; WESTERN BLOTTING;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; BCL-ASSOCIATED DEATH PROTEIN; CASPASE 3; CYTOCHROMES C; DOSE-RESPONSE RELATIONSHIP, DRUG; FLAVONOIDS; GENE EXPRESSION REGULATION, NEOPLASTIC; HEP G2 CELLS; HUMANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOCHONDRIA; POLY(ADP-RIBOSE) POLYMERASES; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIGNAL TRANSDUCTION;

EID: 84898978897     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/1871520613666131125123059     Document Type: Article

References (39)

1. Middleton, E.J.; Kandaswami, C.; Theoharides, T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev., 2000, 52(4), 673-751.
2. Fresco, P.; Borges, F.; Diniz, C.; Marques, M.P. New insights on the anticancer properties of dietary polyphenols. Med. Res. Rev., 2006, 26(6), 747-766.
3. German, J.B.; Walzem, R.L. The health benefits of wine. Annu. Rev. Nutr., 2000, 20, 561-593.
4. Hakkinen, S.H.; Karenlampi, S.O.; Heinonen, I.M.; Mykkanen, H.M.; Torronen, A.R. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J. Agric. Food Chem., 1999, 47, 2274-2279.
5. Sellappan, S.; Akoh, C.C. Flavonoids and antioxidant capacity of Georgiagrown Vidalia onions. J. Agric. Food Chem., 2000, 50, 5338-5442.
6. Leibovitz, B.E.; Mueller, J.A. Bioflavonoids and polyphenols: medical applications. J. Optimal Nutr., 1993, 2: 17-35.
7. Aherne, S.A.; O'Brien, N.M. Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxideinduced DNA damage in Caco-2 and HepG2 cells. Nutr. Cancer, 1999, 34, 160-166.
8. Yanez, J.; Vicente, V.; Alcaraz, M.; Castillo, J.; Benavente-Garcia, O.; Canteras, M.; Teruel, J.A. Cytotoxicity and antiproliferative activities of several phenolic compounds against three melanocytes cell lines: relationship between structure and activity. Nutr. Cancer, 2004, 49, 191-199.
9. Blonska, M.; Czuba, Z.P.; Krol, W. Effect of flavone derivatives on interleukin-1beta (IL-1beta) mRNA expression and IL-1beta protein synthesis in stimulated RAW. 264.7 macrophages. Scand. J. Immunol., 2003, 57, 162-166.
10. Zhang, X.H.; Zou, Z.Q.; Xu, C.W.; Shen, Y.Z.; Li, D. Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex. Molecular Medicine Reports, 2011, 4, 273-277.
11. Thornberry, N.A.; Lazebnik, Y. Caspases: Enemies within. Science, 1998, 281, 1312-1316.
12. Green, D.R.; Reed, J.C. Mitochondria and apoptosis. Science, 1998, 281, 1309-1312.
13. Nicholson, K.; Anderson, N. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal, 2002, 14, 381-395.
14. Ballif, B.; Blenis, J. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Differ., 2001, 12, 397-408.
15. Kuntz, S.; Wenzel, U.; Daniel, H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur. J. Nutr., 1999, 38, 133-142.
16. Zhang, Q.; Zhao, X.H.; Wang, Z.J. Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem. Toxicol., 2008, 46, 2042-2053.
17. Carli, C.B.; de Matos, D.C.; Lopes, F.C.; Maia, D.C.; Dias, M.B.; Sannomiya, M.; Rodrigues, C.M.; Andreo, M.A.; Vilegas, W.; Colombo, L.L.; Carlos, I.Z. Isolated flavonoids against mammary tumour cells LM2. Z. Naturforsch. C., 2009, 64, 32-36.
18. Alexandrakis, M.; Letourneau, R.; Kempuraj, D.; Kandere- Grzybowska, K.; Huang, M.; Christodoulou, S.; Boucher, W.; Seretakis, D.; Theoharides, T.C. Flavones inhibit proliferation and increase mediator content in human leukemic mast cells (HMC-1). Eur. J. Haematol., 2003, 71, 448-454.
19. Yanez, J.; Vicente, V.; Alcaraz, M.; Castillo, J.; Benavente-Garcia, O.; Canteras, M.; Teruel, J.A. Cytotoxicity and antiproliferative activities of several phenolic compounds against three melanocytes cell lines: relationship between structure and activity. Nutr. Cancer, 2004, 49, 191-199.
20. McKay, D.L.; Blumberg, J.B. The role of tea in human health: an update. J. Am. Coll. Nutr., 2002, 21, 1-13.
21. Lotito, S.B.; Frei, B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic. Biol. Med., 2006, 41, 1727-1746.
22. Schutte, M.E.; van de Sandt, J.J.M.; Alink, G.M.; Groten, J.P.; Rietjens, I.M. Myricetin stimulatesthe absorption of the pro-carcinogen PhIP. Cancer Lett., 2006, 231, 36-42.
23. Zou, H.; Li, Y.; Liu, X.; Wang, X. An APAF-1 cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem., 1999, 274, 11549-11556.
24. Baxa, D.M.; Luo, X.; Yoshimura, F.K. Genistein Induces apoptosis in T lymphoma cells via mitochondrial damage. Nutr. Cancer, 2005, 51, 93-101.
25. Haraguchi, M.; Torii, S.; Matsuzawa, S.; Xie, Z.; Kitada, S.; Krajewski, S.; Yoshida, H.; Mak, T.W.; Reed, J.C. Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2. J. Exp. Med., 2000, 191, 1709-1720.
26. Smoot, R.L.; Blechacz, B.R.; Werneburg, N.W.; Bronk, S.F.; Sinicrope, F.A.; Sirica, A.E.; Gores, G.J. A Bax-mediated mechanism for obatoclax-induced apoptosis of cholangiocarcinoma cells. Cancer Res., 2010, 70, 1960-1969.
27. Youle, R.J.; Strasser, A. The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol., 2008, 9, 47-59.
28. Leber, B.; Lin, J.; Andrews, D.W. Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes. Apoptosis, 2007, 12, 897-911.
29. Letai, A.; Bassik, M.C.; Walensky, L.D.; Sorcinelli, M.D.; Weiler, S.; Korsmeyer, S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell, 2002, 2, 183-192.
30. Koh, D.W.; Dawson, T.M.; Dawson, V.L. Mediation of cell death by poly(ADP-ribose) polymerase-1. Pharmacol. Res., 2005, 52, 5-14.
31. El-Serag, H.B.; Rudolph, K.L. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis. Gastroenterology, 2007, 132, 2557-2576.
32. Hu, T.H.; Huang, C.C.; Lin, P.R.; Chang, H.W.; Ger, L.P.; Lin, Y.W.; Changchien, C.S.; Lee, C.M.; Tai, M.H. Expression and prognostic role of tumor suppressor gene PTEN/ MMAC1/TEP1 in hepatocellular carcinoma. Cancer, 2003, 97, 1929-1940.
33. Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug. Discov., 2009, 8, 627-644.
34. Lindsley, C.W. The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation: a 2009 update. Curr. Top. Med. Chem., 2010, 10, 458-477.
35. Datta, S.R.; Dudek, H.; Tao, X.; Masters, S.; Fu, H.; Gotoh, Y.; Greenberg, M.E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 1997, 91, 231-241.
36. Delpeso, L.; Gonzalez-Garcia, M.; Page, C.; Herrera, R.; Nunez, G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science, 1997, 278(5338), 687-689.
37. Zha, J.; Harada, H.; Yang, E.; Jockel, J.; Korsmeyer, S.J. Serine phosporylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-XL. Cell, 1996, 87, 619-628.
38. Shao, J.L.; Wan, X. H.; Chen, Y.; Bi, C.; Chen, H.M.; Zhong, Y.; Heng X.H.; Qian J.Q. H2S protects hippocampal neurons from anoxia-reoxygenation through cAMP-mediated PI3K/Akt/p70S6K cell-survival signaling pathways. J. Mol. Neurosci, 2011, 43, 453-460.
39. Mitsui, H.; Takuwa, N.; Maruyama, T.; Maekawa, H.; Hirayama, M.; Sawatari, T.; Hashimoto, N.; Takuwa, Y.; Kimura, S. The MEK1-ERK MAP kinase pathway and the PI 3-kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver cancer cells. Int. J. Cancer, 2001, 92, 55-62.