Journal
BRITISH JOURNAL OF NUTRITION
Volume 100, Issue 1, Pages 36-43Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0007114508882979
Keywords
maslinic acid; oleanolic acid; apoptosis; HT-29 cells
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We have previously reported the anticarcinogenic effects of an olive fruit extract composed of pentacyclic triterpenes, the main components of which are maslinic acid (73.25%) and oleanolic acid (25.75%). Here we examined the effects of the individual components on proliferation, necrosis and apoptosis rates by fluorescence-based techniques in human HT-29 colon cancer cells. Oleanolic acid showed moderate antiproliferative activity, with an EC50 of 160.6 (SE 10.6) mu mol/l, and moderate cytotoxicity at high concentrations (>= 250 mu mol/l). On the other hand, maslinic acid inhibited cell growth with an EC50 of 101.2 (SE 7.8) mu mol/l, without necrotic effects. Oleanolic acid, which lacks a hydroxyl group at the carbon 2 position, failed to activate caspase-3 as a prime apoptosis protease. In contrast, maslinic acid increased caspase-3-like activity at 10, 25 and 50 mu mol/l by 3, 3.5- and 5-fold over control cells, respectively. The detection of ROS in the mitochondria, which serve as pro-apoptotic signal, evidenced the different bioactivity of the two triterpenes. Confocal microscopy analysis revealed that maslinic acid generated superoxide anions while oleanolic acid-treated cells did not differ from the control. Completion of apoptosis by maslinic acid was confirmed microscopically by the increase in plasma membrane permeability, and detection of DNA fragmentation. In conclusion, the anticancer activity observed for olive fruit extracts seems to originate from maslinic acid but not from oleanolic acid. Maslinic acid therefore is a promising new compound for the chemoprevention of colon cancers.
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