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
Carcinogenesisjournal_title
Carcinogenesisauthors
Chau MN,El Touny LH,Jagadeesh S,Banerjee PPdoi
10.1093/carcin/bgm148subject
Has Abstractpub_date
2007-11-01 00:00:00pages
2282-90issue
11eissn
0143-3334issn
1460-2180pii
bgm148journal_volume
28pub_type
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