(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

FEBS Lett. 2006 Nov 27;580(27):6302-10. doi: 10.1016/j.febslet.2006.10.038. Epub 2006 Oct 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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