TY - JOUR
T1 - Effects of genistein on the polyamine metabolism and cell growth in DLD-1 human colon cancer cells
AU - Linsalata, Michele
AU - Russo, Francesco
AU - Notarnicola, Maria
AU - Guerra, Vito
AU - Cavallini, Aldo
AU - Clemente, Caterina
AU - Messa, Caterina
PY - 2005
Y1 - 2005
N2 - 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 μM 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. Box and Bcl-2 gene expressions were evaluated by multiplex-polymerase chain reaction. At concentration ≥1 μM, genistein decreased significantly the ODC activity and the polyamine levels. At the same concentration, genistein also increased significantly Box mRNA expression, but not Bcl-2 mRNA expression. Higher concentrations (≥10 μM) 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.
AB - 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 μM 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. Box and Bcl-2 gene expressions were evaluated by multiplex-polymerase chain reaction. At concentration ≥1 μM, genistein decreased significantly the ODC activity and the polyamine levels. At the same concentration, genistein also increased significantly Box mRNA expression, but not Bcl-2 mRNA expression. Higher concentrations (≥10 μM) 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.
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U2 - 10.1207/s15327914nc5201_11
DO - 10.1207/s15327914nc5201_11
M3 - Article
C2 - 16091008
AN - SCOPUS:24144487119
VL - 52
SP - 84
EP - 93
JO - Nutrition and Cancer
JF - Nutrition and Cancer
SN - 0163-5581
IS - 1
ER -