title: Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines.
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.
authors.affiliation: School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Kent Street, Bentley, Western Australia, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Mahoney
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.forename: Pierra
authors.initials: P
authors.lastname: Rogers
authors.forename: Susan
authors.initials: S
authors.lastname: Hisheh
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Arun
authors.initials: A
authors.lastname: Dharmarajan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007529:Isoflavones / Q000633:toxicity*; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D017931:DNA Primers; D007529:Isoflavones; C471183:phenoxodiol; D053148:Caspase 3