Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

Abstract

The incidence of intestinal cancer is high in Western populations but is relatively uncommon in Asia and Africa (Boyle et al, 1985). It is thought that this variation in incidence is strongly influenced by diet (Armstrong and Doll, 1975;Adlercreutz, 1990) and it is estimated that about 32% of deaths by all cancers, and 70% of deaths from colorectal cancer, could be prevented by a change in diet (Willet, 1995). There is also evidence to suggest that a high intake of soya-based foods (as in populations of Southeast Asia) could contribute to a reduced incidence of mammary (Lee et al, 1995) and prostate (Severson et al 1989) cancer.Soya beans are an abundant source of the isoflavones genistein, daidzein and glyceitin (Wang and Murphy, 1994). These diphenol molecules are structurally similar to the steroidal oestrogens and thus, have been termed phyto-oestrogens. Due to this similarity, attention has focused on the role of phyto-oestrogens in preventing both hormonally mediated (particularly breast) and hormonally independent cancers. Soya metabolites may reduce the risk of colon cancers (Messina et al, 1994). Genistein in particular possesses several anti-tumorigenic activities in vitro, including inhibition of angiogenesis (Fotsis et al, 1993), topoisomerase (Okura et al, 1988) and tyrosine kinase (Ogawara et al, 1989) activity, in addition to having antioxidant properties (Wei et al, 1993). Experiments using colon cancer cell lines have shown that genistein, and the related isoflavone biochanin A, can inhibit cell proliferation and induce apoptosis (Yanagihara et al, 1993;Kuo, 1996), again implying protective effects.No data are available to demonstrate the effects of isoflavones on normal intestinal cell lines. In this study we aimed to investigate the proliferative and apoptotic effects of genistein in vitro on normal intestinal epithelial cells and compare these to the effects on malignant cell lines. We also aimed to examine the effects of some novel isoflavones, which have been synthesized primarily as specific tyrosine kinase inhibitors, upon the same cell lines. The effects of these isoflavones are compared with the effects of oestradiol, the anti-oestrogen tamoxifen, and the specific tyrosine kinase inhibitor, tyrphostin. MATERIALS AND METHODS Cell culture methodsIEC18 and IEC6 cells, related clones isolated from normal neonatal rat small intestine, were originally obtained from A Quaroni (Quaroni and May, 1980). In all assays these lines were used below passage 20. SW620 and HT29 human colon adenocarcinoma lines were obtained from the English Tissue Culture Collection (ETCC, Porton Down, Wilts, UK). All cells were maintained and passaged in Dulbecco's modified Eagles medium (DMEM) (GibcoBRL, Paisley, UK) containing 5% fetal calf serum (FCS) (Sigma, Poole, UK), 0.25 U ml -1 insulin (Hypurin, Fisons, Loughborough, UK), 100 U ml -1 penicillin and 30 µg ml -1 streptomycin (all Sigma, Poole, UK). Charcoal-stripped FCS, phenol red free DMEM, genistein, biochanin A, oestradiol, tamoxifen and tyrphostin 25 were a...

Genistein Inhibits Intestinal Cell Proliferation in Piglets

“…The inhibition of intestinal cellular proliferation by genistein in vivo supports that observed in vitro by our group (22) and others (19,20,44). In vitro studies have delineated a possible mechanism underlying the biphasic effects of genistein for cell proliferation.…”

Effect of genistein on cholesterol metabolism-related genes in a colon cancer cell line

“…Our findings support a variety of studies that have linked the soy-derived isoflavones, such as genistein, with antitumorigenic activity [6,12]. Genistein has been demonstrated to reduce proliferation and induce G2/M phase arrest and apoptotic death in colon cancer HT-29 cells [40].…”

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

“…Among flavonoids, phytoestrogen genistein has drawn attention in recent years due to a variety of biological activities that may account for its cancer-preventive effects. In vitro experiments demonstrated that genistein influences proliferation, differentiation and apoptosis in different tumor cell types (85). The anticancer effects of genistein involve inhibition of angiogenesis, topoisomerase, tyrosine kinase activity and antioxidant processes (86).…”