Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

Abstract

Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7β-hydroxysitosterol (7β-OHsito) versus 7β-hydroxycholesterol (7β-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 μM 7β-OHsito or to 30 μM 7β-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7β-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7β-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 7β-OHsito-induced apoptotic process but not that triggered by 7β-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death. © 2005 Nature Publishing Group All rights reserved.