Euphorbia and Momordica metabolites for overcoming multidrug resistance

摘要

Multidrug resistance (MDR) is the major obstacle for cancer chemotherapy. MDR is a multifactorial phenomenon that can result from several mechanisms, including an increased drug efflux, due to overexpression of P-glycoprotein (P-gp) that transports anticancer drugs out of the cells. Thus, the role of this transporter has made it a therapeutic target and the development of P-gp modulators considered among the most realistic approaches for overcoming P-gp-mediated MDR. Many other strategies have been proposed. One of them is the identification of compounds that selectively kill multidrug resistant cells. In our search for MDR modulators from plants, the P-gp inhibition ability of a large number of compounds on resistant cancer cells was evaluated. These compounds, presented in this review, comprise mainly diterpenes, triterpenes and phenolic derivatives. The most relevant results were obtained from two sets of compounds: macrocyclic diterpenes with the jatrophane and lathyrane scaffold, and triterpenes of the cucurbitane-type isolated from Euphorbia species and Momordica balsamina L., respectively. Additionally, some of those macrocyclic diterpenes, and ent-abietane diterpenic lactones, also isolated from Euphorbia species, were found to be selectively toxic to drug-resistant phenotypes.