efflux of drugs in the cell membrane by ATP-binding cassette (ABC) transporters [1]. Normally, cancer cells overexpress ABC transporters, which include P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which limit drug accumulation within the cell. Therefore, inhibiting ABC transporters is often 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 many molecules, including nitric oxide (NO). NO is a totally free radical that plays a biphasic part in cancer cells based on its concentration. Low concentrations of NO promote cancer cell proliferation and progression by the Warburg effect, when larger 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, 13,2 ofX protein (BAX), and BCL-2 homologous antagonist killer (BAK) pathways [80]. Researchers have attempted to deliver higher concentrations of NO straight or by way of NO donors for cancer remedy. Benefits indicate that NO inhibits not merely the MDR impact by hindering ATPase activity, but in addition cancer cell growth [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 merchandise 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 talked about above, high concentration of NO inhibits ABC transporters, that are accountable for MDR in cancer [13,18]. GL also has an MDR reduction effect by itself, rising cellular uptake by means of opening of tight junctions and inhibiting efflux of drugs from cancer cells [19,20]. Within this review, we describe GL as a potential MDR inhibitor in cancer chemotherapy that exerts its MDR protective effects by inhibiting ABC transporters by way of NO regulation. Use of GL in chemotherapy could be an efficient, non-toxic approach to growing NO availability within the cancer microenvironment compared to direct delivery of NO or NO donors. 2. Multidrug Resistance in Cancer Chemotherapy The most widespread cancer remedy methods are surgery, radiotherapy, and chemotherapy. Every single system is often applied alone or in combination determined by cancer sort, stage, and patient condition. Even though surgery HSPA5 Formulation usually is employed because the key process to treat cancer, extra strategies are necessary for comprehensive mAChR5 drug removal of cancer. Radiotherapy, which requires the use of high doses of radiation to remove cancer, may be utilised to treat regional cancer. On the other hand, like surgery, radiotherapy can’t eliminate the possibility of metastatic cancer. Chemotherapy refers to administration of anti-cancer drugs including antimetabolites, genotoxic drugs, and mitosis inhibitors to control proliferation and promote apoptosis of cancer cells. In fact, chemotherapy is usually applied to treat several cancer forms such as metastatic cancer, which can be restricted in other methods [5,21,22]. 2.