Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

SIMPLE SUMMARY: Glycyrrhizin (GL) has anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant activity. In particular, GL reduces multidrug resistance (MDR) in cancer cells, which is a major obstacle to chemotherapy. Nitric oxide (NO) also plays an important role in MDR, and GL affects NO concentration in the tumor microenvironment. However, the effects of GL and NO interaction on MDR have not been reviewed. Here, we review the role of GL as an NO regulator in cancer cells and its subsequent anti-MDR effect and posit that GL is a promising MDR inhibitor for cancer chemotherapy. ABSTRACT: Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism of MDR. Recent studies have suggested that nitric oxide (NO) can be used to overcome MDR by inhibiting the ATPase function of ATP-dependent pumps. Several attempts have been made to deliver NO to the tumor microenvironment (TME), however there are limitations in delivery. Glycyrrhizin (GL), an active compound of licorice, has been reported to both reduce the MDR effect by inhibiting ATP-dependent pumps and function as a regulator of NO production in the TME. In this review, we describe the potential role of GL as an NO regulator and MDR inhibitor that efficiently reduces the MDR effect in cancer chemotherapy.