Effects of Genistein on the Polyamine Metabolism and Cell Growth in DLD-1 Human Colon Cancer Cells

Abstract

Polyamines and their rate-limiting enzyme, ornithine decarboxylase (ODC), are actively involved in cell growth and differentiation. The phytoestrogen genistein has been demonstrated to possess antitumor properties by influencing proliferation, differentiation, and apoptosis. The aim of this study was to investigate the effects of genistein at concentrations ranging from 0.01 to 100 microM on the polyamine biosynthesis, cell proliferation, and apoptosis in the estrogen receptor-positive DLD-1 human colon cancer cell line. Polyamine levels and ODC activity were evaluated by high performance liquid chromatography and radiometric technique, respectively. The proliferative response was estimated by [3H]-thymidine incorporation and the colorimetric 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Apoptosis was investigated by DNA fragmentation. Bax and Bcl-2 gene expressions were evaluated by multiplex-polymerase chain reaction. At concentration >or=1 microM, genistein decreased significantly the ODC activity and the polyamine levels. At the same concentration, genistein also increased significantly Bax mRNA expression, but not Bcl-2 mRNA expression. Higher concentrations (>or=10 microM) were needed to obtain a significant inhibition of cell proliferation and DNA fragmentation. The results of this study suggest that genistein can affect growth of DLD-1 cells by both decreasing polyamine biosynthesis and inducing apoptosis. However, further studies are required to assess the true ability of a soy rich diet in modifying colon cancer risk.

Estrogen Stimulates the Expression of Mismatch Repair Gene hMLH1 in Colonic Epithelial Cells

“…We speculate that when E2 level is low, the proliferation activity of colonic epithelial cells may override the effect of E2 on hMLH1 expression. It has been reported that estrogen can inhibit colonic epithelial cell proliferation (14)(15)(16). This is consistent with our observation that estrogen level correlated negatively with cell proliferation marker PCNA expression.…”

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

“…Research by our group investigated the effects on the polyamine biosynthesis and cell growth following administration of increasing concentrations of genistein (from 0.01 µM up to 100 µM) in the DLD-1 human colon cancer cells (88). This cell line has the peculiarity of being ER-positive.…”

Gene polymorphisms in the ornithine decarboxylase–polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations

“…Although the need for NQO1 at high isoflavone concentration was increased, the NQO1 rs1800566 T allele encoded low activity of NQO1, and NQO1 encoded by the T allele reduces the function of ODC, leading to decreased polyamine synthesis. Moreover, isoflavone is directly involved in decreasing ODC activity [7]. ODC inhibition by isoflavone alone and low NQO1 enzymatic activity caused by the rs1800566 T allele can result in decreased polyamine synthesis.…”

“…The isoflavone genistein participates directly in inhibition of ODC activity and decreases polyamine levels [7]. It has been suggested that the interaction between genetic variants of enzymes in the ODC-polyamine synthesis pathway and isoflavone might be involved in modifying gastric cancer risk.…”