Journal
BIOCHIMIE
Volume 95, Issue 11, Pages 2157-2167Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2013.08.017
Keywords
Maslinic acid; Triterpenes; Colon cancer cells; Extrinsic apoptotic pathway
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Funding
- Consejeria de Tecnologia e Innovacion of the Andalucian regional government
- Spanish government [AGL2006-12210-C03-02/ALI, SAF2005-01627, ISCIII-RTICC (RD06/0020/0046)]
- AGAUR-Generalitat de Catalunya [2009SGR1308, 2009 CTP 00026]
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We report that a novel triterpenoid, (2a,3b)-2,3-dihydroxyolean-12-en-28-oic acid (maslinic acid), isolated from olive pomace from Olea europaea, triggers primarily the extrinsic and later the intrinsic apoptotic pathways in Caco-2 human colon-cancer cells. Apoptosis induced by maslinic acid was confirmed by FACS analysis using annexine-V FICT staining. This induction of apoptosis was correlated with the early activation of caspase-8 and caspase-3, the activation of caspase-8 was also correlated with higher levels of Bid cleavage and decreased Bcl-2, but with no change in Bax expression. Maslinic acid also induced a sustained activation of c-Jun N-terminal kinase (JNK). Incubation with maslinic acid also resulted in the later activation of caspase-9, which, together with the lack of any Bax activation, suggests that the mitochondrial pathway is not required for apoptosis induced by maslinic acid in this cell line. In this study we found that the mechanism of apoptotic activation in p53-deficient Caco-2 cells differs significantly from that found in HT-29 cells. Natural agents able to activate both the extrinsic and intrinsic apoptotic pathways by avoiding the mitochondrial resistance mechanisms may be useful for treatment against colon cancer regardless of its aetiology. (C) 2013 Elsevier Masson SAS. All rights reserved.
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