The reversal of antineoplastic drug resistance in cancer cells by β-elemene

Abstract

Multidrug resistance (MDR), defined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, significantly limits the efficacy of antitumor drugs. A major mechanism that mediates MDR in cancer is the overexpression of adenosine triphosphate (ATP)-binding cassette transporters. These transporters bind to their respective substrates and catalyze their efflux from cancer cells, thereby lowering the intracellular concentrations of the substrates and thus attenuating or even abolishing their efficacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen-activated protein kinase pathway. In this review, we discuss the mechanisms by which β-elemene, a compound extracted from Rhizoma zedoariae that has clinical antitumor efficacy, overcomes drug resistance in cancer.

Fig. 1

Structure of β-elemene

Fig. 2

A schematic model of the mechanisms for β-elemene-induced apoptosis and augmentation of the efficacy of anticancer drugs. β-elemene may enhance the therapeutic effect of anticancer drugs by blocking the substrate efflux function (purple arrows) of the multidrug-resistant transporter P-glycoprotein (P-gp). In addition, it has been proposed that β-elemene may affect multiple pathways to produce apoptosis in tumor cells. Black arrows indicate stimulatory modifications, whereas red arrows indicate inhibitory modifications. XIAP X-linked inhibitor of apoptosis protein, ATP adenosine triphosphate, ADP adenosine diphosphate