Differential effects of deoxycholic acid on proliferation of neoplastic and differentiated colonocytes in vitro.
The secondary bile acid deoxycholic acid is believed to be a promoter of large bowel cancer, in part by inducing colonic epithelial proliferation. The effects of deoxycholic acid on [3H]thymidine incorporation by the human colon cancer cell line HT29 and two differentiated subclones were measured and compared. The subclone HT29-C1 has features of mature absorptive cells and HT29-N2 cells secrete mucus under cholinergic control. The three cell lines were treated with deoxycholic acid (DCA) at concentrations of 0, 5, 10, 50, 100, 150, and 300 microM for 3, 6, 9, 15, 24, and 48 hr. A significant increase in proliferation was noted in HT29 cells only at 6 hr with 5 and 10 microM deoxycholic acid. Neither the subclone HT29-C1, nor HT29-N2 cells exhibited significant change in [3H]thymidine incorporation with DCA at these concentrations or time points. Higher doses of deoxycholic acid above 50 microM and duration of exposure greater than 24 hr were cytotoxic to all three cell lines. The proliferative effects of DCA in HT29 cells were not paralleled by changes in protein kinase C activity or protein kinase C isoform expression. Quantitative and qualitative differences in PKC isoform expression were not noted in the three cell lines used in this study. The proliferative effects of DCA on HT29 cells appear to be independent of the PKC signal transduction pathway.
Peiffer
L P
LP
Department of Medicine, University Hospital, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Peters
D J
DJ
McGarrity
T J
TJ
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013936:Thymidine; D014316:Tritium; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D003840:Deoxycholic Acid; D014316:Tritium; D011493:Protein Kinase C; D013936:Thymidine