Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor

Biochemical and Biophysical Research Communications

Volumn 406, Issue 2, 2011, Pages 194-199

  Van Aller, Glenn S ^a   Carson, Jeff D ^a   Tang, Wei ^b   Peng, Hao ^b   Zhao, Lin ^b   Copeland, Robert A ^a   Tummino, Peter J ^a   Luo, Lusong ^b  

^a GLAXOSMITHKLINE   (United States)

^b BioDuro LLC   (China)

Author keywords

AKT; Cancer; EGCG; Kinase inhibitor; MTOR; PI3K

Indexed keywords

ANTINEOPLASTIC AGENT; EPIGALLOCATECHIN GALLATE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST TUMOR; CANCER CELL; CANCER INHIBITION; CELL PROLIFERATION; DRUG BINDING; DRUG POTENCY; HUMAN; HUMAN CELL; MOLECULAR DOCKING; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TEA;

ANTINEOPLASTIC AGENTS; CATECHIN; CELL PROLIFERATION; HEK293 CELLS; HUMANS; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; TEA; TOR SERINE-THREONINE KINASES;

MAMMALIA;

EID: 79952440161     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2011.02.010     Document Type: Article

References (32)

1. Khan N., Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008, 269:269-280.
2. Nagle D.G., Ferreira D., Zhou Y.D. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry 2006, 67:1849-1855.
3. Shankar S., Ganapathy S., Srivastava R.K. Green tea polyphenols: biology and therapeutic implications in cancer. Front Biosci. 2007, 12:4881-4899.
4. Ahn W.S., Yoo J., Huh S.W., Kim C.K., Lee J.M., Namkoong S.E., Bae S.M., Lee I.P. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur. J. Cancer Prev. 2003, 12:383-390.
5. J. McLarty, R.L. Bigelow, M. Smith, D. Elmajian, M. Ankem, J.A. Cardelli, Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro, Cancer Prev. Res. (Phila Pa) 2, (2009) 673-682.
6. Yap T.A., Garrett M.D., Walton M.I., Raynaud F., de Bono J.S., Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr. Opin. Pharmacol. 2008, 8:393-412.
7. 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.
8. Brachmann S., Fritsch C., Maira S.M., Garcia-Echeverria C. PI3K and mTOR inhibitors: a new generation of targeted anticancer agents. Curr. Opin. Cell Biol. 2009, 21:194-198.
9. Carson J.D., Van A.G., Lehr R., Sinnamon R.H., Kirkpatrick R.B., Auger K.R., Dhanak D., Copeland R.A., Gontarek R.R., Tummino P.J., Luo L. Effects of oncogenic p110alpha subunit mutations on the lipid kinase activity of phosphoinositide 3-kinase. Biochem. J. 2008, 409:519-524.
10. Van Aller G.S., Carson J.D., Fernandes C., Lehr R., Sinnamon R.H., Kirkpatrick R.B., Tummino P.J., Luo L. Characterization of PI3K class IA isoforms with regulatory subunit p55alpha using a scintillation proximity assay. Anal. Biochem. 2008, 383:311-315.
11. Engelman J.A. Targeting PI3K signalling in cancer: opportunities challenges and limitations. Nat. Rev. Cancer 2009, 9:550-562.
12. Alessi D.R., Pearce L.R., Garcia-Martinez J.M. New insights into mTOR signaling: mTORC2 and beyond. Sci. Signal. 2009, 2:e27.
13. Huang J., Manning B.D. A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem. Soc. Trans. 2009, 37:217-222.
14. Marcussen M., Larsen P.J. Cell cycle-dependent regulation of cellular ATP concentration and depolymerization of the interphase microtubular network induced by elevated cellular ATP concentration in whole fibroblasts. Cell Motil. Cytoskeleton 1996, 35:94-99.
15. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101.
16. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947.
17. McMenamin M.E., Soung P., Perera S., Kaplan I., Loda M., Sellers W.R. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 1999, 59:4291-4296.
18. Wu G., Xing M., Mambo E., Huang X., Liu J., Guo Z., Chatterjee A., Goldenberg D., Gollin S.M., Sukumar S., Trink B., Sidransky D. Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res. 2005, 7:R609-R616.
19. Kim M.J., Kim H.I., Chung J., Jeong T.S., Park H.R. (-)-Epigallocatechin-3-gallate (EGCG) increases the viability of serum-starved A549 cells through its effect on Akt. Am. J. Chin. Med. 2009, 37:723-734.
20. Natsume H., Adachi S., Takai S., Tokuda H., Matsushima-Nishiwaki R., Minamitani C., Yamauchi J., Kato K., Mizutani J., Kozawa O., Otsuka T. (-)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt pathway in osteoblasts. Int. J. Mol. Med. 2009, 24:197-203.
21. Qin J., Xie L.P., Zheng X.Y., Wang Y.B., Bai Y., Shen H.F., Li L.C., Dahiya R. A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochem. Biophys. Res. Commun. 2007, 354:852-857.
22. Walker E.H., Pacold M.E., Perisic O., Stephens L., Hawkins P.T., Wymann M.P., Williams R.L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell 2000, 6:909-919.
23. J. McLarty, R.L. Bigelow, M. Smith, D. Elmajian, M. Ankem, J.A. Cardelli, Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro, Cancer Prev. Res. (Phila Pa) 2 (2009) 673-682.
24. Yang C.S., Lambert J.D., Ju J., Lu G., Sang S. Tea and cancer prevention: molecular mechanisms and human relevance. Toxicol. Appl. Pharmacol. 2007, 224:265-273.
25. Kapetanovic I.M., Crowell J.A., Krishnaraj R., Zakharov A., Lindeblad M., Lyubimov A. Exposure and toxicity of green tea polyphenols in fasted and non-fasted dogs. Toxicology 2009, 260:28-36.
26. Foster D.R., Sowinski K.M., Chow H.H., Overholser B.R. Limited sampling strategies to estimate exposure to the green tea polyphenol epigallocatechin gallate, in fasting and fed conditions. Ther. Drug Monit. 2007, 29:835-842.
27. Isbrucker R.A., Edwards J.A., Wolz E., Davidovich A., Bausch J. Safety studies on epigallocatechin gallate (EGCG) preparations, Part 3: Teratogenicity and reproductive toxicity studies in rats. Food Chem. Toxicol. 2006, 44:651-661.
28. Wan X., Harkavy B., Shen N., Grohar P., Helman L.J. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 2007, 26:1932-1940.
29. O'Reilly K.E., Rojo F., She Q.B., Solit D., Mills G.B., Smith D., Lane H., Hofmann F., Hicklin D.J., Ludwig D.L., Baselga J., Rosen N. MTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006, 66:1500-1508.
30. Chiarini F., Fala F., Tazzari P.L., Ricci F., Astolfi A., Pession A., Pagliaro P., McCubrey J.A., Martelli A.M. Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia. Cancer Res. 2009, 69:3520-3528.
31. Serra V., Markman B., Scaltriti M., Eichhorn P.J., Valero V., Guzman M., Botero M.L., Llonch E., Atzori F., Di C.S., Maira M., Garcia-Echeverria C., Parra J.L., Arribas J., Baselga J. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res. 2008, 68:8022-8030.
32. Maira S.M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., Brachmann S., Chene P., De P.A., Schoemaker K., Fabbro D., Gabriel D., Simonen M., Murphy L., Finan P., Sellers W., Garcia-Echeverria C. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol. Cancer Ther. 2008, 7:1851-1863.