(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid, a new natural triterpene from Olea europea, induces caspase dependent apoptosis selectively in colon adenocarcinoma cells.

Abstract

Triterpenoids are known to induce apoptosis and to be anti-tumoural. Maslinic acid, a pentacyclic triterpene, is present in high concentrations in olive pomace. This study examines the response of HT29 and Caco-2 colon-cancer cell lines to maslinic-acid treatment. At concentrations inhibiting cell growth by 50-80% (IC50HT29=61+/-1 microM, IC80HT29=76+/-1 microM and IC50Caco-2=85+/-5 microM, IC80Caco-2=116+/-5 microM), maslinic acid induced strong G0/G1 cell-cycle arrest and DNA fragmentation, and increased caspase-3 activity. However, maslinic acid did not alter the cell cycle or induce apoptosis in the non-tumoural intestine cell lines IEC-6 and IEC-18. Moreover, maslinic acid induced cell differentiation in colon adenocarcinoma cells. These findings support a role for maslinic acid as a tumour suppressant and as a possible new therapeutic tool for aberrant cell proliferation in the colon. In this report, we demonstrate for the first time that, in tumoural cancer cells, maslinic acid exerts a significant anti-proliferation effect by inducing an apoptotic process characterized by caspase-3 activation by a p53-independent mechanism, which occurs via mitochondrial disturbances and cytochrome c release.

• Authors: Fernando J Reyes, Josep J Centelles, José A Lupiáñez, Marta Cascante
• Journal: FEBS letters (FEBS Lett) Vol. 580 Issue 27 Pg. 6302-10 (Nov 27 2006) ISSN: 0014-5793 [Print] England
• PMID: 17083937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Triterpenes
• Tumor Suppressor Protein p53
• Cytochromes c
• maslinic acid
• Caspase 3

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, metabolism)
• Cytochromes c (metabolism)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Humans
• Mitochondria (metabolism)
• Olea (chemistry)
• Triterpenes (chemistry, pharmacology, therapeutic use)
• Tumor Suppressor Protein p53 (metabolism)