Effects of genistein on the polyamine metabolism and cell growth in DLD-1 human colon cancer cells.
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.
Linsalata
Michele
M
Laboratory of Biochemistry, Scientific Institute for Digestive Diseases, IRCCS Saverio de Bellis, Castellana G, (BA), Italy. irccsbiochimica@libero.it
Russo
Francesco
F
Notarnicola
Maria
M
Guerra
Vito
V
Cavallini
Aldo
A
Clemente
Caterina
C
Messa
Caterina
C
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011874:Radiometry; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; C494826:BAX protein, human; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019833:Genistein