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.
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Abbreviations
- 7β-OHchol:
-
7β-hydroxycholesterol
- 7β-Ohsito:
-
7β-hydroxy sitosterol
- PI:
-
propidium iodide
- HMG-CoA reductase:
-
3-hydroxy-methylglutaryl coenzyme A reductase
- DMSO:
-
dimethyl sulfoxide
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Acknowledgements
We are grateful to Dr. Nikolaus Seiler for advice and critical reading of the manuscript. This work was supported by a grant from the Ministère de la Jeunesse, de l'Education Nationale et de la Recherche, France (RARE 015 No. 02 P 0641).
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Roussi, S., Winter, A., Gosse, F. et al. Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells. Cell Death Differ 12, 128–135 (2005). https://doi.org/10.1038/sj.cdd.4401530
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DOI: https://doi.org/10.1038/sj.cdd.4401530
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