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

摘要

We reported previously that 7β-hydroxysitosterol and 7β-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7β-hydroxysitosterol but not by 7β-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 7β-hydroxycholesterol treated cells, but not with 7β-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 7β-hydroxysitosterol was significantly more active on than 7β-hydroxycholesterol. Both hydroxysterols induced apoptosis by mitochondrial membrane permeabilization. However, 7β-hydroxycholesterol exhibited a specific enhancement of oxidative stress and of endonuclease G expression despite its closely related chemical structure with 7β-hydroxysitosterol. The two hydroxysterols exhibit different lipophilic properties which may explain their different biological effects.