Selenomethionine inhibits growth and suppresses cyclooxygenase-2 (COX-2) protein expression in human colon cancer cell lines.
Currently, selenium (in the form of high selenium containing yeast or selenomethionine) is being evaluated for anticancer effects against both human colon polyp recurrence and human prostate cancer, respectively. Chemical speciation analysis of the high selenium containing yeast indicates that selenomethionine (SeMet) is a major constituent of selenized yeast. We tested the hypothesis that SeMet might affect colon cancer cell growth by mechanisms involving cyclooxygenases (COX). The growth of all four-colon cancer cell lines tested was inhibited by selenomethionine. Furthermore, selenomethionine decreased COX-2 protein and PGE2 levels in HCA-7 cells. Selenomethionine suppressed COX-2 RNA levels in HCA-7 cells which could account for decreased COX-2 protein levels. Finally, the addition of PGE2 protected cells from the antiproliferative effects of selenomethionine in a concentration dependent manner. Selenomethionine might regulate COX-2 at the transcriptional level. These data suggests that Se-Met-induced cell growth inhibition may be, in part, mediated by COX-2 dependent mechanisms. The results of this study support the use of selenium agents in colon cancer chemoprevention trials.
Baines
Antonio
A
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
Taylor-Parker
Michele
M
Goulet
Anne-Christine
AC
Renaud
Christian
C
Gerner
Eugene W
EW
Nelson
Mark A
MA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012645:Selenomethionine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone