Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines

Journal of biosciences

David Brown¹  Susan Hisheh²  Arun Dharmarajan2⁵  Frank Arfuso⁵  Pierra Rogers⁵  Simon Mahoney³  Michael Millward⁴ 

[1] Novogen Limited, 140 Wicks Road, North Ryde, NSW, Australia 2113$$;Department of Medicine – Austin Health and Northern Health, The University of Melbourne, Parkville, Victoria, Australia 3010$$;School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Kent Street, Bentley, Western Australia, Australia 6102$$;School of Medicine and Pharmacology, The University of Western Australia, Perth, Western Australia, Australia 6009$$;School of Anatomy & Human Biology, The University of Western Australia, Perth, Western Australia, Australia 6009$$

关键词: Apoptosis;    isoflavone;    phenoxodiol;    prostate;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

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.

【 授权许可】

Unknown