Suchergebnisse

5 pages, 1 table. ; Natural polyphenolic compounds from plants and fruits have been reported to be potent antioxidants and to present antitumoral properties. The difficulty to clearly identify structure/antitumoral activity of this family of compounds makes difficult to optimize the formulation of combinations of polyphenolic extracts from different plants or fruits to achieve the best antitumoral potency. Recent advances have been achieved in this field from the exhaustive characterization of polyphenolic extracts with different degree of polymerization and percentage of galloylation. Here we review the results obtained in this field from our team (Lizarraga et al., 2007; Lozano et al., 2006; Lozano et al., 2005; Matito et al., 2003; Tourino et al., 2008; Tourino et al., 2005) that relate degree of polymerization and galloylation to radical scavenging capacity, tumor cell proliferation inhibition and induction of apoptosis. From this review we concluded that natural polyphenolic extract with high degree of polymerization and galloylation will present the higher antiproliferative and induction of apoptosis capacities. ; This work was supported by Spanish Government and the European Union FEDER funds (SAF2005-01627 and AGL2004-07579-C04-03/ALI) and ISCIII-RTICC (RD06/0020/0046); Generalitat de Catalunya (2005SGR00204; 2006ITT-10007). ; Peer reviewed

[Background] Maslinic acid, a pentacyclic triterpene found in the protective wax-like coating of the leaves and fruit of Olea europaea L., is a promising agent for the prevention of colon cancer. We have shown elsewhere that maslinic acid inhibits cell proliferation to a significant extent and activates mitochondrial apoptosis in colon cancer cells. In our latest work we have investigated further this compound's apoptotic molecular mechanism. [Methods] We used HT29 adenocarcinoma cells. Changes genotoxicity were analyzed by single-cell gel electrophoresis (comet assay). The cell cycle was determined by flow cytometry. Finally, changes in protein expression were examined by western blotting. Student's t-test was used for statistical comparison. [Results] HT29 cells treated with maslinic acid showed significant increases in genotoxicity and cell-cycle arrest during the G0/G1 phase after 72 hours' treatment and an apoptotic sub-G0/G1 peak after 96 hours. Nevertheless, the molecular mechanism for this cytotoxic effect of maslinic acid has never been properly explored. We show here that the anti-tumoral activity of maslinic acid might proceed via p53-mediated apoptosis by acting upon the main signaling components that lead to an increase in p53 activity and the induction of the rest of the factors that participate in the apoptotic pathway. We found that in HT29 cells maslinic acid activated the expression of c-Jun NH2-terminal kinase (JNK), thus inducing p53. Treatment of tumor cells with maslinic acid also resulted in an increase in the expression of Bid and Bax, repression of Bcl-2, release of cytochrome-c and an increase in the expression of caspases -9, -3, and -7. Moreover, maslinic acid produced belated caspase-8 activity, thus amplifying the initial mitochondrial apoptotic signaling. [Conclusion] All these results suggest that maslinic acid induces apoptosis in human HT29 colon-cancer cells through the JNK-Bid-mediated mitochondrial apoptotic pathway via the activation of p53. Thus we propose a plausible sequential molecular mechanism for the expression of the different proteins responsible for the intrinsic mitochondrial apoptotic pathway. Further studies with other cell lines will be needed to confirm the general nature of these findings. ; This study was supported by grants BIO157 from the Andalucian regional government; SAF2008-00164 and ISCIII-RTICC (RD06/0020/0046) grants from the Spanish national government and & European Regional Development Fund (ERDF) "Una manera de hacer Europa" and by AGAUR-Generalitat de Catalunya grant 2009SGR1308, 2009 CTP 00026 and Icrea Academia award 2010 granted to M. Cascante).