TY - JOUR
T1 - Sphingomyelin protects against apoptosis and hyperproliferation induced by deoxycholate
T2 - Potential implications for colon cancer
AU - Moschetta, A.
AU - Portincasa, Piero
AU - Van Erpecum, K. J.
AU - Debellis, L.
AU - Vanberge-Henegouwen, G. P.
AU - Palasciano, G.
N1 - Funding Information:
For this project, A.M. received a grant from the Società Italiana di Medicina Interna (SIMI) and Aventis Foundation for best research project for young investigators, year 2000. Drs. Moschetta and Portincasa contributed equally to the work.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - High fecal deoxycholate levels may promote colonic cancer. Phospholipids protect against bile salt-induced cytotoxicity. We therefore aimed to examine whether the dietary phospholipid sphingomyelin could decrease hyperproliferation induced by deoxycholate. In CaCo2 cells, hyperproliferation (by bromodeoxyuridine assay), phosphorylation state of cellular proteins, and apoptosis with concomitant caspase-3 activity were evaluated after incubation with 50-500 μM deoxycholate, with or without sphingomyelin. At 2 and 4 hr of incubation, deoxycholate induced dose-dependent apoptosis, with concomitant caspase-3 activation. At 16 hr, apoptosis had decreased markedly, but there was dose-dependent hyperproliferation (with changed phosphorylation status of cellular proteins) at this time point. Sphingomyelin dose-dependently reduced deoxycholate-induced apoptosis and hyperproliferation. In conclusion, sphingomyelin reduces deoxycholate-induced hyperproliferation and apoptosis. These findings may have implications for colonic cancer prevention by dietary modification.
AB - High fecal deoxycholate levels may promote colonic cancer. Phospholipids protect against bile salt-induced cytotoxicity. We therefore aimed to examine whether the dietary phospholipid sphingomyelin could decrease hyperproliferation induced by deoxycholate. In CaCo2 cells, hyperproliferation (by bromodeoxyuridine assay), phosphorylation state of cellular proteins, and apoptosis with concomitant caspase-3 activity were evaluated after incubation with 50-500 μM deoxycholate, with or without sphingomyelin. At 2 and 4 hr of incubation, deoxycholate induced dose-dependent apoptosis, with concomitant caspase-3 activation. At 16 hr, apoptosis had decreased markedly, but there was dose-dependent hyperproliferation (with changed phosphorylation status of cellular proteins) at this time point. Sphingomyelin dose-dependently reduced deoxycholate-induced apoptosis and hyperproliferation. In conclusion, sphingomyelin reduces deoxycholate-induced hyperproliferation and apoptosis. These findings may have implications for colonic cancer prevention by dietary modification.
KW - Bile salts
KW - Colon cancer
KW - Phospholipids
KW - Prevention
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U2 - 10.1023/A:1023712712025
DO - 10.1023/A:1023712712025
M3 - Article
C2 - 12822868
AN - SCOPUS:0038541971
SN - 0163-2116
VL - 48
SP - 1094
EP - 1101
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 6
ER -