Protection of human colon epithelial cells against deoxycholate by rottlerin.
The bile salt, deoxycholate (DOC), can harm cells and cause disease. Hence, there is interest in identifying compounds capable of protecting cells against DOC. In HCT-116 colon epithelial cells, DOC increased generation of reactive oxygen species and caused DNA damage and apoptosis. These effects of DOC were inhibited by rottlerin, which is a phenolic compound of plant origin. In elucidating its mechansim, rottlerin prevented the release of cytochrome c from mitochondria into cytosol, and also prevented the cleavage of caspase-3. Yet, rottlerin by itself markedly decreased mitochondrial membrane potential and increased mitochondrial superoxide production, but this did not result in cytochrome c release or in caspase-3 cleavage. At a higher test concentration, two other phenolic phytochemicals, namely, quercetin and resveratrol, were each able to largely prevent the occurrence of apoptosis in cells exposed to DOC. In contrast, epigallocatechin gallate, curcumin, and genistein were ineffective.
Longpre
Jennifer M
JM
Cellular and Molecular Nutrition Research Laboratory, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
Loo
George
G
D000098:Acetophenones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003106:Colon / Q000166:cytology*; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000737:chemistry; D003840:Deoxycholic Acid / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology; D010851:Picrates; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D000098:Acetophenones; D001578:Benzopyrans; D001713:Biphenyl Compounds; D004273:DNA, Neoplasm; D006834:Hydrazines; D010636:Phenols; D010851:Picrates; D013267:Stilbenes; D003840:Deoxycholic Acid; D013481:Superoxides; D045304:Cytochromes c; D011794:Quercetin; C004931:1,1-diphenyl-2-picrylhydrazyl; C085746:rottlerin; D053148:Caspase 3; D000077185:Resveratrol