Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7β-hydroxysitosterol and 7β-hydroxycholesterol triggered apoptosis in human colon cancer cells

被引:59
作者
Roussi, Stamatiki
Gosse, Francine
Aoude-Werner, Dalal
Zhang, Xin
Marchioni, Eric
Geoffroy, Philippe
Miesch, Michel
Raul, Francis
机构
[1] IRCAD, Lab Nutr Canc Prevent, F-67091 Strasbourg, France
[2] Univ Strasbourg, INSERM, U682, IRCAD, F-67091 Strasbourg, France
[3] Aerial, F-67300 Schiltigheim, France
[4] ULP, CNRS, UMR 7512, Fac Pharm,Lab Chim Analyt & Sci Aliment, F-67400 Illkirch Graffenstaden, France
[5] ULP, CNRS, UMR 7123, Lab Chim Organ Synthet, F-67008 Strasbourg, France
关键词
apoptosis; Caco-2; cells; 7; beta-hydroxysitosterol; beta-hydroxycholesterol; mitochondria; lysosomes;
D O I
10.1007/s10495-006-0485-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We reported previously that 7 beta-hydroxysitosterol and 7 beta-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7 beta-hydroxysitosterol but not by 7 beta-hydroxycholesterol was related to a caspase-dependent process. In the present report, we compared the effects of both compounds on mitochondria integrity and on various modulators of apoptosis. When Caco-2 cells were exposed to both hydroxysterols, no changes in Bcl-2 and Bax expressions were detected indicating a Bcl-2/Bax-independent cell death pathway, whereas loss of mitochondrial membrane potential and cytochrome c release were observed. Endonuclease G expression and enhanced production of reactive oxygen species were detected in 7 beta-hydroxycholesterol treated cells, but not with 7 beta-hydroxysitosterol. Loss of mitochondrial membrane potential and cell death produced by both hydroxysterols were prevented by vitamin C. Lysosomal membrane integrity was altered with both hydroxysterols, but 7 beta-hydroxysitosterol was significantly more active on than 7 beta-hydroxycholesterol. Both hydroxysterols induced apoptosis by mitochondrial membrane permeabilization. However, 7 beta-hydroxycholesterol exhibited a specific enhancement of oxidative stress and of endonuclease G expression despite its closely related chemical structure with 7 beta-hydroxysitosterol. The two hydroxysterols exhibit different lipophilic properties which may explain their different biological effects.
引用
收藏
页码:87 / 96
页数:10
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