Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review. (September 2021)

• Record Type: Journal Article
• Authors: Memariani, Zahra; Abbas, Syed Qamar; ul Hassan, Syed Shams; Ahmadi, Amirhossein; Chabra, Aroona
• Is Part Of: Pharmacological research. Volume 171(2021)
• Publication Date: 2021-09
• Subjects: NG Naringin -- NGE Naringenin -- LDL Low density lipoprotein -- JAK Jun amino-terminal kinases -- STAT Signal transductor and activator of transcription proteins -- PI3K Phosphatidylinositol-3-kinase -- mTOR mammalian target of rapamycin -- FAK Focal adhesion kinase -- VEGF Vascular endothelial growth factor -- DLL delta-like ligand -- T-ALL T-cell acute lymphoblastic leukemia -- COX Cyclooxygenase -- MAPK Mitogen-activated protein kinases -- ERK extracellular signal-regulated kinases -- MMP matrix metalloproteinase -- RTK receptor tyrosine kinase -- TGF-β Transforming growth factor-β -- BMPs Bone morphogenetic proteins -- GDFs Growth and differentiation factors -- AMH Anti-müllerian hormone -- CEA Carcinoembryonic antigen -- DISC Death-induced signaling complexes -- APAF Apoptotic protease activating factor -- NLCs Nanostructured lipid carriers -- ER Estrogen receptor -- RT-qPCR Real-time quantitative polymerase chain reaction -- UPA Urokinase plasminogen activator -- HCC Hepatocellular carcinoma -- PCNA Proliferating cell nuclear antigen -- EMT Epithelial to mesenchymal transition -- Atg7 Autophagy related 7 -- NEU3 Neuraminidase 3 -- EGFR Epidermal growth factor receptor -- NF-κB nuclear factor- κB; Cancer -- Citrus -- Flavonoid -- Naringin -- Naringenin -- Signal pathways; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105264
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.