TY - JOUR
T1 - Differential effects of deoxycholic acid on proliferation of neoplastic and differentiated colonocytes in vitro
AU - Peiffer, L. P.
AU - Peters, D. J.
AU - Mcgarrity, T. J.
N1 - Funding Information:
Manuscript received De cember 23, 1996; revise d manuscript receive d April 30, 1997; acce pted July 17, 1997. From the De partme nt of Medicine, Unive rsity Hospital, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershe y, Pennsylvaia.n Research sponsored by a grant from the Departmen t of Veterans Affairs Project 001, and grant R29 CA45468 (T.J.M.) from the National Institutes of He alth. Address for reprint requests: Dr. Thomas J. McGarrit, yDivision of Gastroe nterolog, Tyhe Milton S. He rshey Medical Center, The Pennsylvania State Unive rsit, yBox850, He rshey, Pennsylvaia n 17033.
PY - 1997
Y1 - 1997
N2 - 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 μM 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 μM 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 μM 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.
AB - 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 μM 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 μM 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 μM 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.
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U2 - 10.1023/A:1018806431866
DO - 10.1023/A:1018806431866
M3 - Article
C2 - 9398800
AN - SCOPUS:0031451334
SN - 0163-2116
VL - 42
SP - 2234
EP - 2240
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 11
ER -
