Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3.
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.
Chau
My N
MN
Department of Biochemistry and Molecular and Cellular Biology, Medical-Dental Building, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20057, USA.
El Touny
Lara H
LH
Jagadeesh
Shankar
S
Banerjee
Partha P
PP
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D050796:STAT3 Transcription Factor; D019833:Genistein; C509186:TERT protein, human; D019098:Telomerase