The effects of phenoxodiol on the cell cycle of prostate cancer cell lines.
BACKGROUND
Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes.


METHODS
Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30 μM) for 24 and 48 h. The expression of cell cycle genes p21(WAF1), c-Myc, Cyclin-D1, and Ki-67 was investigated by Real Time PCR.


RESULTS
Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21(WAF1) in all the cell lines in response to treatment, indicating that activation of p21(WAF1) and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest.


CONCLUSIONS
Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21(WAF1) and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.
School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Perth, WA 6009 Australia.
Simon
S
Mahoney
School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Perth, WA 6009 Australia ; Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, GPO Box U1987, 6845 Perth, WA Australia.
Frank
F
Arfuso
School of Medicine and Pharmacology, The University of Western Australia, Crawley, Perth, WA 6009 Australia.
Michael
M
Millward
School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Perth, WA 6009 Australia ; Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, GPO Box U1987, 6845 Perth, WA Australia.
Arun
A
Dharmarajan
Cell cycle; Cytotoxicity; Phenoxodiol; Prostate cancer