Different apoptotic mechanisms are involved in the antiproliferative effects of 7beta-hydroxysitosterol and 7beta-hydroxycholesterol in human colon cancer cells.
Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7beta-hydroxysitosterol (7beta-OHsito) versus 7beta-hydroxycholesterol (7beta-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 microM 7beta-OHsito or to 30 microM 7beta-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7beta-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7beta-OHchol did not activate caspase-3 and activation of caspase-9 and DNA fragmentation were delayed. The treatment of cells with the caspase inhibitor Z-VAD.fmk retarded the 7beta-OHsito-induced apoptotic process but not that triggered by 7beta-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.
Roussi
S
S
Laboratoire d'Oncologie Nutritionnelle, Inserm UMR S392/IRCAD, 1, place de l'Hôpital, BP 406, Strasbourg Cedex 67091, France.
Winter
A
A
Gosse
F
F
Werner
D
D
Zhang
X
X
Marchioni
E
E
Geoffroy
P
P
Miesch
M
M
Raul
F
F
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018938:Caco-2 Cells; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D012855:Sitosterols / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006888:Hydroxycholesterols; D012855:Sitosterols; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C011486:hydroxysitosterol; C011724:cholest-5-en-3 beta,7 alpha-diol; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases