Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3.

Abstract:

:Telomerase contributes to the infinite replicative potential of cancer cells by conferring proliferation and survival through the regulation of growth factors and apoptotic proteins. Although it is generally known that the phytoestrogen, genistein, has telomerase-repressing and anti-proliferative effects on various cancer cells at pharmacological concentrations, we report here that physiologically achievable concentrations of genistein enhance telomerase activity, the proliferation of human prostate cancer cells and tumor growth in the transgenic adenocarcinoma mouse prostate model. In determining the mechanism for enhanced telomerase activity, we observed that physiological concentrations of genistein activated signal transducers and activators of transcription 3 (STAT3) both in vitro and in vivo and increased STAT3 binding to the telomerase reverse transcriptase promoter in human prostate cancer cells. These results demonstrate for the first time that physiologically achievable concentrations of genistein enhance telomerase reverse transcriptase transcriptional activity in prostate cancer cells via the activation of STAT3. Consequently, these concentrations of genistein will augment the growth of prostate cancer cells that could be detrimental to individuals with prostate cancer and therefore, caution should be exercised when genistein is considered for chemotherapeutic purposes.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Chau MN,El Touny LH,Jagadeesh S,Banerjee PP

doi

10.1093/carcin/bgm148

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

2282-90

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgm148

journal_volume

28

pub_type

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