Cytotoxic effects of the novel isoflavone,phenoxodiol, on prostate cancer cell lines |
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Authors: | Simon Mahoney Frank Arfuso Pierra Rogers Susan Hisheh David Brown Michael Millward Arun Dharmarajan |
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Institution: | (1) School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Kent Street, Bentley, Western Australia, Australia, 6102;(2) School of Anatomy & Human Biology, The University of Western Australia, Perth, Western Australia, Australia, 6009;(3) Department of Medicine – Austin Health and Northern Health, The University of Melbourne, Parkville, Victoria, Australia, 3010;(4) Novogen Limited, 140 Wicks Road, North Ryde, NSW, Australia, 2113;(5) School of Medicine and Pharmacology, The University of Western Australia, Perth, Western Australia, Australia, 6009; |
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Abstract: | Phenoxodiol is an isoflavone derivative that has been shown to elicit cytotoxic effects against a broad range of human cancers.
We examined the effect of phenoxodiol on cell death pathways on the prostate cell lines LNCaP, DU145 and PC3, representative
of different stages of prostate cancer, and its effects on cell death pathways in these cell lines. Cell proliferation assays
demonstrated a significant reduction in the rate of cell proliferation after 48 h exposure to phenoxodiol (10 and 30 μM).
FACS analysis and 3′-end labelling indicated that all three prostate cancer cell lines underwent substantial levels of cell
death 48 h after treatment. Mitochondrial membrane depolarization, indicative of early-stage cell death signalling, using
JC-1 detection, was also apparent in all cell lines after exposure to phenoxodiol in the absence of caspase-3 activation.
Caspase inhibition assays indicated that phenoxodiol operates through a caspase-independent cell death pathway. These data
demonstrate that phenoxodiol elicits anti-cancer effects in prostate cancer cell lines representative of early and later stages
of development through an as-yet-unknown cell death mechanism. These data warrant the further investigation of phenoxodiol
as a potential treatment for prostate cancer. |
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