Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro.
There have been many reports that high soya-based diets reduce the risk of certain types of cancer. This effect may be due to the presence of high levels of isoflavones derived from the soya bean, particularly genistein which has been shown to be a protein tyrosine kinase (PTK) inhibitor and have both oestrogenic and anti-oestrogenic properties. We have examined the effect of genistein and a number of novel synthetic analogues on both normal (IEC6, IEC18) and transformed (SW620, HT29) intestinal epithelial cell lines. Responses were compared to those elicited by oestradiol, the anti-oestrogen tamoxifen, and the tyrosine kinase inhibitor tyrphostin. Genistein and tamoxifen were potent inhibitors of cell proliferation. Of seven novel isoflavones tested, none were more potent inhibitors than genistein, and all displayed similar relative activities across the different cell lines. In addition to inhibiting cell proliferation, cell death via apoptosis was observed when the cells were exposed to the isoflavones and all but one exhibited PTK inhibitory activity. These data suggest that by reducing proliferation and inducing apoptosis, possibly due in part to PTK inhibition, isoflavones may have a role in protecting normal intestinal epithelium from tumour development (reducing the risk) and may reduce colonic tumour growth.
Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
C
C
Booth
D F
DF
Hargreaves
J A
JA
Hadfield
A T
AT
McGown
C S
CS
Potten
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D007529:Isoflavones / Q000494:pharmacology*; D007941:Leukemia P388 / Q000201:enzymology / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007529:Isoflavones; D020032:Tyrphostins; D013629:Tamoxifen; D011505:Protein-Tyrosine Kinases