efflux of drugs at the cell membrane by ATP-binding cassette (ABC) transporters [1]. Typically, cancer cells overexpress ABC transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which limit drug accumulation inside the cell. Hence, inhibiting ABC transporters might be an efficient way for sensitizing the cancer cells to chemotherapeutic drugs [4]. Several studies have reported attempts to reverse the MDR effect in cancer cells employing a variety of molecules, which includes nitric oxide (NO). NO can be a cost-free radical that plays a biphasic function in cancer cells depending on its concentration. Low concentrations of NO promote cancer cell proliferation and progression by the CDK13 manufacturer Warburg impact, although higher concentrations of NO induce DNA damage and apoptosis in cancer cells by activating the apoptosis signalregulating kinase 1 (ASK1)/c-Jun N-terminal protein kinase (JNK1), BCL-2-associatedCancers 2021, 13, 5762. doi.org/10.3390/cancersmdpi/journal/cancersCancers 2021, 13,two ofX protein (BAX), and BCL-2 homologous antagonist killer (BAK) pathways [80]. Researchers have attempted to provide high concentrations of NO straight or via NO donors for cancer treatment. Benefits indicate that NO inhibits not merely the MDR effect by hindering ATPase activity, but in addition cancer cell development [113]. Even so, NO delivery is restricted by its toxicity and difficulty in attaining optimal concentration [14]. Glycyrrhizin (GL), isolated from Glycyrrhiza glabra (licorice) root, has anti-cancer, antiinflammatory, and anti-oxidant activities. GL enhances NO production from macrophages stimulated with interferon-gamma (IFN-) or lipopolysaccharide (LPS), along with the resulting higher concentration of NO goods kills cancer cells [15,16]. GL upregulates inducible NO synthase (iNOS) by activating the nuclear factor kappa B (NFB) signaling pathway in macrophages [17]. In addition, as mentioned above, high concentration of NO inhibits ABC transporters, that are responsible for MDR in cancer [13,18]. GL also has an MDR reduction impact by itself, COX-3 custom synthesis growing cellular uptake via opening of tight junctions and inhibiting efflux of drugs from cancer cells [19,20]. Within this overview, we describe GL as a potential MDR inhibitor in cancer chemotherapy that exerts its MDR protective effects by inhibiting ABC transporters via NO regulation. Use of GL in chemotherapy will be an efficient, non-toxic approach to escalating NO availability in the cancer microenvironment compared to direct delivery of NO or NO donors. 2. Multidrug Resistance in Cancer Chemotherapy Probably the most frequent cancer remedy methods are surgery, radiotherapy, and chemotherapy. Each approach might be applied alone or in combination based on cancer kind, stage, and patient situation. Although surgery usually is utilized as the principal process to treat cancer, more procedures are expected for full removal of cancer. Radiotherapy, which requires the usage of high doses of radiation to get rid of cancer, could be applied to treat regional cancer. Having said that, like surgery, radiotherapy can not remove the possibility of metastatic cancer. Chemotherapy refers to administration of anti-cancer drugs such as antimetabolites, genotoxic drugs, and mitosis inhibitors to manage proliferation and promote apoptosis of cancer cells. In fact, chemotherapy is often applied to treat several cancer types which includes metastatic cancer, which can be limited in other techniques [5,21,22]. two.