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Different apoptotic mechanisms are involved in the antiproliferative effects of 7beta-hydroxysitosterol and 7beta-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 7beta-hydroxysitosterol (7beta-OHsito) versus 7beta-hydroxycholesterol (7beta-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 microM 7beta-OHsito or to 30 microM 7beta-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7beta-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7beta-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 7beta-OHsito-induced apoptotic process but not that triggered by 7beta-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.
AuthorsS Roussi, A Winter, F Gosse, D Werner, X Zhang, E Marchioni, P Geoffroy, M Miesch, F Raul
JournalCell death and differentiation (Cell Death Differ) Vol. 12 Issue 2 Pg. 128-35 (Feb 2005) ISSN: 1350-9047 [Print] England
PMID15550935 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Hydroxycholesterols
  • Sitosterols
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • hydroxysitosterol
  • cholest-5-en-3 beta,7 alpha-diol
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases
Topics
  • Amino Acid Chloromethyl Ketones (pharmacology)
  • Apoptosis (drug effects, physiology)
  • Caco-2 Cells
  • Caspase 3
  • Caspase 9
  • Caspase Inhibitors
  • Caspases (metabolism)
  • Cell Cycle (drug effects)
  • Cell Proliferation (drug effects)
  • Colonic Neoplasms (pathology)
  • Cysteine Proteinase Inhibitors (pharmacology)
  • DNA Fragmentation (drug effects)
  • Humans
  • Hydroxycholesterols (pharmacology)
  • Sitosterols (pharmacology)

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