Journal Article

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

My N. Chau, Lara H. El Touny, Shankar Jagadeesh and Partha P. Banerjee

in Carcinogenesis

Volume 28, issue 11, pages 2282-2290
Published in print November 2007 | ISSN: 0143-3334
Published online July 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm148
Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3

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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 Article.  6715 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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