Abstract
Simple SummaryGlycyrrhizin (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.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.
Highlights
nitric oxide (NO) produced by inducible NOS (iNOS) of macrophages in tumor microenvironment (TME) reacted with VP-16 leading to decrease of cancer’s cytotoxic effect [117]
They found that GL-induced macrophages produce three times the amount of NO compared to saline-induced macrophages in response to LPS for 48 h
To determine the association between NO and GL, we focus on the relationship between tumor-associated macrophages (TAMs) and GL
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chemotherapy is the most effective method to eradicate cancer, it involves several challenges such as evolution of multidrug resistance (MDR) in cancer cells, which includes altered drug activation due to metabolism and excretion, and increased repair of DNA damage caused by anti-cancer drugs. Inhibiting ABC transporters can be an effective way for sensitizing the cancer cells to chemotherapeutic drugs [4,5,6,7]. Results indicate that NO inhibits the MDR effect by hindering ATPase activity, and cancer cell growth [11,12,13]. GL has an MDR reduction effect by itself, increasing cellular uptake through opening of tight junctions and inhibiting efflux of drugs from cancer cells [19,20]. Use of GL in chemotherapy would be an effective, non-toxic approach to increasing NO availability in the cancer microenvironment compared to direct delivery of NO or NO donors
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