A comparative study of growth-inhibitory effects of isoflavones and their metabolites on human breast and prostate cancer cell lines.
The possible growth-inhibitory properties of the recently synthesized novel metabolite 1-(2,4-dihydrobenzoyl)-1-(4-hydroxyphenyl)ethylene (2-de-O-DMA) and six other metabolites of isoflavones were investigated and compared with those of the major isoflavones genistein, daidzein, and glycitein on human breast noncancer and breast and prostate cancer cell lines in vitro. The novel metabolite 2-de-O-DMA was found to be a more potent inhibitor than genistein on human breast cancer MCF-7, MDA-MB-468, and SK-BR-3 cells and breast noncancer MCF-10A cells. In prostate cancer cell lines, LNCaP and DU145, 2-de-O-DMA elicited a six- to sevenfold more potent inhibition than genistein. Flow cytometric analysis showed that 2-de-O-DMA and genistein blocked cells at the G2/M phase of the cell cycle. Genistein and 2-de-O-DMA led to apoptosis of a variety of cancer cell lines. The rapid response of growth inhibition induced by 2-de-O-DMA compared with genistein strongly suggests that the observed antiproliferation effects elicited by this novel metabolite are mediated via a biological pathway different from that induced by genistein. 2-de-O-DMA, a novel metabolite of isoflavone, could have a potential role in chemopreventive and chemotherapeutic treatment of hormonal breast and prostate cancers.
Xiang
Hong
H
Ray Williams Institute of Paediatric Endocrinology and Diabetes and Metabolism, Children's Hospital, at Westmead, Westmead NSW 2145, Sydney, Australia.
Schevzov
Galina
G
Gunning
Peter
P
Williams
He M
HM
Silink
Martin
M
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D007529:Isoflavones; D019833:Genistein