Dietary flavonoid fisetin: A novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management

Biochemical Pharmacology

Volumn 84, Issue 10, 2012, Pages 1277-1281

  Adhami, Vaqar Mustafa ^a   Syed, Deeba Nadeem ^a   Khan, Naghma ^a   Mukhtar, Hasan ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Cancer; Fisetin; mTOR; PI3K Akt; Prostate

Indexed keywords

BETA CATENIN; CYCLIN D1; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; FISETIN; GELATINASE A; INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAPAMYCIN; TESTOSTERONE;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; APPLE; AUTOPHAGY; CANCER GROWTH; CATALYSIS; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE M PHASE; CELL ORGANELLE; CELL PROLIFERATION; CELL VIABILITY; COMPETITIVE INHIBITION; CORRELATION ANALYSIS; CUCUMBER; DIET; DOWN REGULATION; DRUG MECHANISM; ENZYME ACTIVITY; GRAPE; HUMAN; KIWIFRUIT; LIPID PEROXIDATION; LIVER CELL CARCINOMA; LUNG ADENOCARCINOMA; LUNG CANCER; LUNG CARCINOGENESIS; MELANOMA; MICROGLIA; NERVE CELL DIFFERENTIATION; NERVE CELL NECROSIS; NONHUMAN; OXIDATIVE STRESS; PANCREAS CANCER; PERSIMMON; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW; RNA INTERFERENCE; STRAWBERRY;

ANIMALS; CELL LINE, TUMOR; FLAVONOIDS; FRUIT; HUMANS; MALE; PHOSPHATIDYLINOSITOL 3-KINASES; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; TOR SERINE-THREONINE KINASES; VEGETABLES;

EID: 84867865103     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2012.07.012     Document Type: Review

References (49)

1. N. Khan, F. Afaq, and H. Mukhtar Cancer chemoprevention through dietary antioxidants: progress and promise Antioxid Redox Signal 10 2008 475 510
2. Y.J. Moon, X. Wang, and M.E. Morris Dietary flavonoids: effects on xenobiotic and carcinogen metabolism Toxicol In Vitro 20 2006 187 210
3. Y.J. Surh Cancer chemoprevention with dietary phytochemicals Nat Rev Cancer 3 2003 768 780
4. M. Kimira, Y. Arai, K. Shimoi, and S. Watanabe Japanese intake of flavonoids and isoflavonoids from foods J Epidemiol 8 1998 168 175
5. C.S. Shia, S.Y. Tsai, S.C. Kuo, Y.C. Hou, and P.D. Chao Metabolism and pharmacokinetics of 3,3′,4′,7-tetrahydroxyflavone (fisetin), 5-hydroxyflavone, and 7-hydroxyflavone and antihemolysis effects of fisetin and its serum metabolites J Agric Food Chem 57 2009 83 89
6. P. Maher, K.F. Salgado, J.A. Zivin, and P.A. Lapchak A novel approach to screening for new neuroprotective compounds for the treatment of stroke Brain Res 1173 2007 117 125
7. K. Ishige, D. Schubert, and Y. Sagara Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms Free Radic Biol Med 30 2001 433 446
8. M. Gabor, and E. Eperjessy Antibacterial effect of fisetin and fisetinidin Nature 212 1966 1273
9. Y. Sagara, J. Vanhnasy, and P. Maher Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation J Neurochem 90 2004 1144 1155
10. P. Maher, T. Akaishi, and K. Abe Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory Proc Natl Acad Sci USA 103 2006 16568 16573
11. L.T. Zheng, J. Ock, B.M. Kwon, and K. Suk Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity Int Immunopharmacol 8 2008 484 494
12. B. Sung, M.K. Pandey, and B.B. Aggarwal Fisetin, an inhibitor of cyclin-dependent kinase 6, down-regulates nuclear factor-kappaB-regulated cell proliferation, antiapoptotic and metastatic gene products through the suppression of TAK-1 and receptor-interacting protein-regulated IkappaBalpha kinase activation Mol Pharmacol 71 2007 1703 1714
13. Y.S. Touil, A. Fellous, D. Scherman, and G.G. Chabot Flavonoid-induced morphological modifications of endothelial cells through microtubule stabilization Nutr Cancer 61 2009 310 321
14. A.L. Salmela, J. Pouwels, A. Varis, A.M. Kukkonen, P. Toivonen, and P.K. Halonen Dietary flavonoid fisetin induces a forced exit from mitosis by targeting the mitotic spindle checkpoint Carcinogenesis 30 2009 1032 1040
15. Y.C. Chen, S.C. Shen, W.R. Lee, H.Y. Lin, C.H. Ko, and C.M. Shih Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1 Arch Toxicol 76 2002 351 359
16. W.R. Lee, S.C. Shen, H.Y. Lin, W.C. Hou, L.L. Yang, and Y.C. Chen Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied by a decrease of reactive oxygen species, and activation of caspase 3 and Ca(2+)-dependent endonuclease Biochem Pharmacol 63 2002 225 236
17. Y.C. Liao, Y.W. Shih, C.H. Chao, X.Y. Lee, and T.A. Chiang Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549 J Agric Food Chem 57 2009 8933 8941
18. N. Ravichandran, G. Suresh, B. Ramesh, and G.V. Siva Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice Food Chem Toxicol 49 2011 1141 1147
19. Y. Suh, F. Afaq, J.J. Johnson, and H. Mukhtar A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways Carcinogenesis 30 2009 300 307
20. W.S. Chen, Y.J. Lee, Y.C. Yu, C.H. Hsaio, J.H. Yen, and S.H. Yu Enhancement of p53-mutant human colorectal cancer cells radiosensitivity by flavonoid fisetin Int J Radiat Oncol Biol Phys 77 2010 1527 1535
21. X. Lu, J. Jung, H.J. Cho, D.Y. Lim, H.S. Lee, and H.S. Chun Fisetin inhibits the activities of cyclin-dependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells J Nutr 135 2005 2884 2890
22. S.H. Yu, P.M. Yang, C.W. Peng, Y.C. Yu, and S.J. Chiu Securin depletion sensitizes human colon cancer cells to fisetin-induced apoptosis Cancer Lett 300 2011 96 104
23. I. Murtaza, V.M. Adhami, B.B. Hafeez, M. Saleem, and H. Mukhtar Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB Int J Cancer 125 2009 2465 2473
24. R.A. Hiipakka, H.Z. Zhang, W. Dai, Q. Dai, and S. Liao Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols Biochem Pharmacol 63 2002 1165 1176
25. A.Q. Haddad, N. Fleshner, C. Nelson, B. Saour, M. Musquera, and V. Venkateswaran Antiproliferative mechanisms of the flavonoids 2,2′-dihydroxychalcone and fisetin in human prostate cancer cells Nutr Cancer 62 2010 668 681
26. F. Afaq, N. Zaman, N. Khan, D.N. Syed, S. Sarfaraz, and M.A. Zaid Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables Int J Cancer 123 2008 1508 1515
27. N. Khan, F. Afaq, D.N. Syed, and H. Mukhtar Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells Carcinogenesis 29 2008 1049 1056
28. N. Khan, M. Asim, F. Afaq, M. Abu Zaid, and H. Mukhtar A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice Cancer Res 68 2008 8555 8563
29. C.S. Chien, K.H. Shen, J.S. Huang, S.C. Ko, and Y.W. Shih Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells Mol Cell Biochem 333 2010 169 180
30. Y. Suh, F. Afaq, N. Khan, J.J. Johnson, F.H. Khusro, and H. Mukhtar Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells Carcinogenesis 31 2010 1424 1433
31. S.N. Malik, M. Brattain, P.M. Ghosh, D.A. Troyer, T. Prihoda, and R. Bedolla Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer Clin Cancer Res 8 2002 1168 1171
32. M.E. McMenamin, P. Soung, S. Perera, I. Kaplan, M. Loda, and W.R. Sellers Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage Cancer Res 59 1999 4291 4296
33. C.L. Kremer, R.R. Klein, J. Mendelson, W. Browne, L.K. Samadzedeh, and K. Vanpatten Expression of mTOR signaling pathway markers in prostate cancer progression Prostate 66 2006 1203 1212
34. D. Gioeli Signal transduction in prostate cancer progression Clin Sci (Lond) 108 2005 293 308
35. D. Gioeli, J.W. Mandell, G.R. Petroni, H.F. Frierson Jr., and M.J. Weber Activation of mitogen-activated protein kinase associated with prostate cancer progression Cancer Res 59 1999 279 284
36. M.T. Abreu-Martin, A. Chari, A.A. Palladino, N.A. Craft, and C.L. Sawyers Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer Mol Cell Biol 19 1999 5143 5154
37. H. Gao, X. Ouyang, W.A. Banach-Petrosky, W.L. Gerald, M.M. Shen, and C. Abate-Shen Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer Proc Natl Acad Sci USA 103 2006 14477 14482
38. A.R. Uzgare, and J.T. Isaacs Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus normal prostate epithelial cells Cancer Res 64 2004 6190 6199
39. C.W. Kinkade, M. Castillo-Martin, A. Puzio-Kuter, J. Yan, T.H. Foster, and H. Gao Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model J Clin Invest 118 2008 3051 3064
40. N. Khan, F. Afaq, F.H. Khusro, V. Mustafa Adhami, Y. Suh, and H. Mukhtar Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin Int J Cancer 130 2012 1695 1705
41. R. Zoncu, A. Efeyan, and D.M. Sabatini mTOR: from growth signal integration to cancer, diabetes and ageing Nat Rev Mol Cell Biol 12 2011 21 35
42. D.A. Guertin, and D.M. Sabatini Defining the role of mTOR in cancer Cancer Cell 12 2007 9 22
43. R.J. Dowling, I. Topisirovic, T. Alain, M. Bidinosti, B.D. Fonseca, and E. Petroulakis mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs Science 328 2010 1172 1176
44. M.M. Webber, S.T. Quader, H.K. Kleinman, D. Bello-DeOcampo, P.D. Storto, and G. Bice Human cell lines as an in vitro/in vivo model for prostate carcinogenesis and progression Prostate 47 2001 1 13
45. V. Adhami, R.K. Lall, and H. Mukhtar Fisetin, a dietary flavonoid and a novel mTOR inhibitor, for treatment and prevention of prostate cancer [Abstract] Proceedings of the 102nd annual meeting of the American association for cancer research March 31-April 4, 2012, Chicago, IL 2012 AACR Philadelphia (PA)
46. R. Tripathi, T. Samadder, S. Gupta, A. Surolia, and C. Shaha Anticancer activity of a combination of cisplatin and fisetin in embryonal carcinoma cells and xenograft tumors Mol Cancer Ther 10 2011 255 268
47. C. Kandaswami, E. Perkins, D.S. Soloniuk, G. Drzewiecki, and E. Middleton Jr. Ascorbic acid-enhanced antiproliferative effect of flavonoids on squamous cell carcinoma in vitro Anticancer Drugs 4 1993 91 96
48. Y.S. Touil, J. Seguin, D. Scherman, and G.G. Chabot Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice Cancer Chemother Pharmacol 68 2011 445 455
49. E. Szliszka, K.J. Helewski, E. Mizgala, and W. Krol The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells Int J Oncol 39 2011 771 779