Triterpenoids as antiproliferative agents in classical and atypical multidrug resistant cancer cells

Abstract

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, results from altered cell membrane transport due to overexpression of transporter proteins that act as efflux pumps, such as P-glycoprotein (Pgp/MDR1). Conversely, MDR cells without overexpression of transporter proteins are referred as atypical MDR cells and their resistance has been associated with altered DNA topoisomerase II. Topoisomerases are nuclear enzymes crucial to DNA replication, transcription, and recombination. According to some authors, atypical MDR may result from altered expression of some metabolizing enzymes [1]. Therefore, a promising approach to overcome MDR is the development of compounds that are selectively cytotoxic to resistant cancer cells. The aim of this work was to evaluate the antiproliferative activity of several cucurbitane-type triterpenoids (Fig. 2) isolated from Momordica balsamina (Fig. 1), a medicinal African plant also used as food, in three human drug-sensitive cancer cell lines: gastric, pancreatic and colon carcinomas, and in classical and atypical multidrug resistant sublines .