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Modulation of phosphatidylinositol‐3‐kinase/protein kinase B‐ and mitogen‐activated protein kinase‐pathways by tea polyphenols in human prostate cancer cells
Author(s) -
Siddiqui Imtiaz Ahmad,
Adhami Vaqar Mustafa,
Afaq Farrukh,
Ahmad Nihal,
Mukhtar Hasan
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10737
Subject(s) - du145 , lncap , protein kinase b , pi3k/akt/mtor pathway , cancer research , protein kinase a , kinase , prostate cancer , mapk/erk pathway , chemistry , signal transduction , pharmacology , biology , cancer , biochemistry , medicine
We have earlier shown that oral infusion of a polyphenolic fraction isolated from green tea, at a human achievable dose (equivalent to six cups of green tea per day), significantly inhibits prostate cancer (PCA) development and metastasis in tr ansgenic a denocarcinoma of m ouse p rostate (TRAMP) model that closely mimics progressive form of human prostatic disease (Gupta et al. [2001]: Proc. Natl. Acad. Sci. U.S.A. 98:10350–10355.). A complete understanding of the mechanism(s) and molecular targets of PCA chemopreventive effects of tea polyphenols may be useful in developing novel approaches for its prevention. In this study, we employed two distinct human PCA cell lines viz. DU145 (androgen‐unresponsive prostate carcinoma cells) and LNCaP (androgen‐responsive prostate carcinoma cells) and, employing immunoblot analysis, we evaluated the effect of epigallocatechin‐3‐gallate (EGCG), the major polyphenol present in green tea and theaflavins (TF), the major polyphenol present in black tea on phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (PKB) and mitogen‐activated protein kinase (MAPK) pathways. Both EGCG and TF treatment were found to (i) decrease the levels of PI3K and phospho‐Akt and (ii) increase Erk1/2 in both DU145 and LNCaP cells. Our data showing the inhibition of the constitutive levels of PI3K and the phosphorylation of Akt could be important because the treatment approaches should be aimed at the inhibition of the constitutive levels of PI3K and Akt. Our data also suggest that Erk1/2 could be involved in the anti‐cancer effects of EGCG and TF. Taken together, our study, for the first time demonstrated the modulation of the constitutive activation of PI3K/Akt and Erk1/2 pathways by EGCG as well as TF. We suggest that detailed studies in appropriate tumor model system are needed to establish the relevance of the cell culture work to in vivo models. © 2003 Wiley‐Liss, Inc.