Sphingomyelin protects against apoptosis and hyperproliferation induced by deoxycholate: potential implications for colon cancer.
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 microM 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.
Moschetta
A
A
Department of Internal and Public Medicine, Section of Internal Medicine, University of Bari Medical School, Bari, Italy.
Portincasa
P
P
van Erpecum
K J
KJ
Debellis
L
L
Vanberge-Henegouwen
G P
GP
Palasciano
G
G
D017209:Apoptosis; D018938:Caco-2 Cells / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000517:prevention & control; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D013109:Sphingomyelins / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D004792:Enzyme Precursors; D013109:Sphingomyelins; D003840:Deoxycholic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases