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(2α,3β)‐2,3‐Dihydroxyolean‐12‐en‐28‐oic acid, a new natural triterpene from Olea europea , induces caspase dependent apoptosis selectively in colon adenocarcinoma cells
Author(s) -
Reyes Fernando J.,
Centelles Josep J.,
Lupiáñez José A.,
Cascante Marta
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.10.038
Subject(s) - apoptosis , triterpene , chemistry , dna fragmentation , cell cycle checkpoint , cell cycle , biochemistry , cell growth , cytochrome c , programmed cell death , cancer research , biology , medicine , alternative medicine , pathology
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 μM, IC80HT29 = 76 ± 1 μM and IC50Caco‐2 = 85 ± 5 μM, IC80Caco‐2 = 116 ± 5 μM), 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.