Abstract |
We reported previously that 7beta-hydroxysitosterol and 7beta-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7beta-hydroxysitosterol but not by 7beta-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 7beta-hydroxycholesterol treated cells, but not with 7beta-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 7beta-hydroxysitosterol was significantly more active on than 7beta-hydroxycholesterol. Both hydroxysterols induced apoptosis by mitochondrial membrane permeabilization. However, 7beta-hydroxycholesterol exhibited a specific enhancement of oxidative stress and of endonuclease G expression despite its closely related chemical structure with 7beta-hydroxysitosterol. The two hydroxysterols exhibit different lipophilic properties which may explain their different biological effects.
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Authors | Stamatiki Roussi, Francine Gossé, Dalal Aoudé-Werner, Xin Zhang, Eric Marchioni, Philippe Geoffroy, Michel Miesch, Francis Raul |
Journal | Apoptosis : an international journal on programmed cell death
(Apoptosis)
Vol. 12
Issue 1
Pg. 87-96
(Jan 2007)
ISSN: 1360-8185 [Print] Netherlands |
PMID | 17136497
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BAX protein, human
- Hydroxycholesterols
- Proto-Oncogene Proteins c-bcl-2
- Reactive Oxygen Species
- Sitosterols
- bcl-2-Associated X Protein
- hydroxysitosterol
- cholest-5-en-3 beta,7 alpha-diol
- Cytochromes c
- Endodeoxyribonucleases
- endonuclease G
- Ascorbic Acid
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Topics |
- Apoptosis
(drug effects, physiology)
- Ascorbic Acid
(pharmacology)
- Caco-2 Cells
- Colonic Neoplasms
(drug therapy, metabolism, pathology)
- Cytochromes c
(metabolism)
- Endodeoxyribonucleases
(metabolism)
- Humans
- Hydroxycholesterols
(pharmacology)
- Lysosomes
(drug effects, metabolism)
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects, metabolism)
- Oxidative Stress
(drug effects)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Sitosterols
(pharmacology)
- bcl-2-Associated X Protein
(metabolism)
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