Triterpenoids as antiproliferative agents in classical and atypical multidrug resistant cancer cells
Resistance of cancer cells to multiple classes of structurally and mechanistically unrelated antitumor drugs can be defined as multidrug resistance (MDR), and it is one of the major causes of chemotherapy failure. The most significant mechanism of MDR, referred as typical or classical MDR, is that resulting from altered cell membrane transport due to over-expression of the transporter protein P-glycoprotein (Pgp/MDR1) that act as an drug efflux pump. Conversely, MDR cells without overexpression of this transporter protein are referred as atypical MDR cells and their resistance has been associated with enhanced expression of alternative transporter protreins, altered DNA topoisomerase II activity or other mechanisms. According to some authors, atypical MDR may also result from altered expression of some metabolizing enzymes . Therefore, a promising approach to overcome MDR is the development of compounds that are selectively cytotoxic to resistant cancer cells. Continuing our search for anticancer agents from plant sources , the aim of this work was to evaluate the antiproliferative activity of several cucurbitane-type triterpenoids, isolated from Momordica balsamina a medicinal African plant also used as food. The study was carried out with human cancer cell lines derived from three tumor entities: gastric (EPG85–257), pancreatic (EPP85–181) and colon (HT-29) carcinomas. Furthermore, different multidrug-resistant variants of these cancer cell lines with over-expression of MDR1/P-gp or no MDR1/P-gp expression were also investigated. When comparing with the parental cell lines, some of the multidrug resistant variants showed increased sensitivities to the studied compounds.
Acknowledgements: The authors wish to thank the Science and Technology Foundation, (FCT, grant SFRH/BD/22321/2005).
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