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Dihydrotestosterone sensitises LNCaP cells to death induced by epigallocatechin‐3‐gallate (EGCG) or an IGF‐i receptor inhibitor
Author(s) -
Thomas Francis,
Patel Suril,
Holly Jeff M.P.,
Persad Raj,
Bahl Amit,
Perks Claire M.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20873
Subject(s) - du145 , lncap , apoptosis , prostate cancer , dihydrotestosterone , androgen receptor , endocrinology , medicine , cell growth , growth inhibition , biology , cancer research , programmed cell death , androgen , cancer , biochemistry , hormone
BACKGROUND Compelling evidence has accumulated for chemopreventive effects for the active component of green tea Epigallocatechin‐3‐Gallate (EGCG) particularly for prostate cancer (CaP). METHODS We have assessed interactions between the effects of EGCG and two main regulators of prostate cell function, dihydrotestosterone (DHT) and insulin‐like growth factor‐1 (IGF‐I). Using LNCaP (androgen‐sensitive), PC3 and DU145 (androgen‐resistant) CaP cell lines, we assessed the effect of EGCG alone on growth (0–200 µM) and on cell death (0–50 µM). RESULTS EGCG decreased the proliferation of all the CaP cancer cells in a dose‐dependent manner with an increase in apoptosis from 30 to 50 µM. With DU145 cells, a sub‐apoptotic dose of EGCG (10–20 µM) reduced IGF‐induced growth. With LNCaP cells, a sub‐apoptotic dose of EGCG (8 µM) switched DHT from a growth promoter to a growth inhibitor. A similar reversal of DHT effect was seen in the presence of an IGF‐I receptor inhibitor, AG1024 (1 µM). These responses appeared to be due to DHT sensitizing the cells to apoptosis by EGCG and AG1024 ( P < 0.01 and P < 0.001 respectively). CONCLUSIONS Our data suggests that both green tea and AG1024 are effective in inhibiting cell growth and inducing death in CaP cells but the effects of both are more effective in the presence of androgen. Prostate 69: 219–224, 2009. © 2008 Wiley–Liss, Inc.