British Journal of Nutrition

Full Papers

Antiproliferative and apoptosis-inducing effects of maslinic and oleanolic acids, two pentacyclic triterpenes from olives, on HT-29 colon cancer cells

M. Emília Juana1, Joana M. Planasa1 c1, Valentina Ruiz-Gutierreza2, Hannelore Daniela3 and Uwe Wenzela4

a1 Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, Barcelona E-08028, Spain

a2 Nutrición y Metabolismo Lipídico, Instituto de la Grasa, CSIC, Av. Padre Garcia Tejero 4, Sevilla E-41012, Spain

a3 Molecular Nutrition Unit, Department of Food and Nutrition, Technical University of Munich, Am Forum 5, Freising D-85350, Germany

a4 Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Lieberg-University of Giessen, Heinrich-Buff Ring 26-32, Giessen D-35392, Germany

Abstract

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) μmol/l, and moderate cytotoxicity at high concentrations ( ≥ 250 μmol/l). On the other hand, maslinic acid inhibited cell growth with an ec50 of 101·2 (se 7·8) μmol/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 μmol/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.

(Received May 15 2007)

(Revised October 23 2007)

(Accepted October 25 2007)

(Online publication December 26 2008)

Correspondence:

c1 Corresponding author: Dr Joana M. Planas, fax +34 93 403 59 01, email jmplanas@ub.edu

Footnotes

Abbreviations: DMSO, dimethyl sulphoxide; ROS, reactive oxygen species

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