Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition

Medicinal value of natural products comes from symbiotic and competitive evolution in Earth’s complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.