Overcoming Multidrug Resistance in Cancer Chemotherapy by Natural Products

Cancer is the second leading cause of death in the world after heart disease. One of themajor obstacles in clinical cancer chemotherapy is multidrug resistance (MDR). Severalmechanisms can mediate the development of MDR, including increased drug efflux from thecells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathwaystowards apoptosis. Cancer cells can develop resistance to entire classes of drugs withsimilar mechanisms of action or become cross resistant to drugs which are structurally andmechanistically unrelated. Unfortunately, progress to restore drug sensitivity in multidrugresistantcancer cells by synthetic modulators has been slow and challenging. Therefore, inrecent years many researchers turned their attention to utilizing natural products that areusually non-toxic and are well tolerated in the human body, to combat this resistance.Inhibitors or modulators originating from natural sources have a great diversity includingbiologically active components that are extracted from plants, bacteria, fungi and even marineorganisms. For instance, curcumin and flavonoids are two of the most popular naturalproducts that modulate ABC drug transporters. In addition, many other plant secondarymetabolites (SMs) such as limonoids, steroids, polyphenols, and alkaloids also canpotentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. Inthis review we will focus on the most popular natural products which have a potential tomodulate multidrug resistance and so they can be suggested as new adjuvants to traditionalchemotherapy drugs to improve cancer patient treatment.

کلیدواژه ها:

Multidrug Resistance ، Cancer ، Natural Products ، Secondary Metabolites ، Drug Transporter