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Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

Summary 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...

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Published in:British Journal of Cancer 1999-07, Vol.80 (10), p.1550-1557
Main Authors: Booth, C, Hargreaves, D F, Hadfield, J A, McGown, A T, Potten, C S
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description Summary 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.
doi_str_mv 10.1038/sj.bjc.6690559
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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. 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Abdomen</subject><subject>Humans</subject><subject>Intestinal Mucosa - cytology</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Isoflavones - pharmacology</subject><subject>Leukemia P388 - enzymology</subject><subject>Leukemia P388 - pathology</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Protein-Tyrosine Kinases - antagonists &amp; inhibitors</subject><subject>Rats</subject><subject>Regular</subject><subject>regular-article</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Intestinal Mucosa - cytology</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Isoflavones - pharmacology</topic><topic>Leukemia P388 - enzymology</topic><topic>Leukemia P388 - pathology</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Protein-Tyrosine Kinases - antagonists &amp; inhibitors</topic><topic>Rats</topic><topic>Regular</topic><topic>regular-article</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. 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source Wiley-Blackwell Read & Publish Collection; PubMed Central
subjects Animals
Apoptosis - drug effects
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Division - drug effects
Colonic Neoplasms - pathology
Drug Resistance
Enzyme Inhibitors - pharmacology
Epidemiology
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Intestinal Mucosa - cytology
Intestinal Mucosa - drug effects
Isoflavones - pharmacology
Leukemia P388 - enzymology
Leukemia P388 - pathology
Medical sciences
Molecular Medicine
Oncology
Protein-Tyrosine Kinases - antagonists & inhibitors
Rats
Regular
regular-article
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tamoxifen - pharmacology
Tumor Cells, Cultured
Tumors
Tyrphostins - pharmacology
title Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro
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