Traditional Medicine and History of Medical Sciences Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, Pakistan.
Pharmacol Res. 2021 Sep;171:105264. doi: 10.1016/j.phrs.2020.105264. Epub 2020 Nov 6.
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.
虽然西方国家的许多癌症发病率得到了控制，但由于发展和社会问题导致的风险因素增加，一些癌症（如肺癌、乳腺癌和结直肠癌）的发病率在许多中低收入国家目前正在上升。此外，内源性因素（如遗传突变、类固醇激素、胰岛素和胰岛素样生长因子系统、炎症、氧化应激和外源性因素（包括烟草、酒精、传染病原体和辐射））被认为会损害细胞功能并导致癌变。化疗、手术、放射治疗、激素治疗和靶向治疗是癌症治疗中使用的一些方法。然而，各种短期和长期的副作用也会根据与治疗相关的临床因素对患者的预后产生重大影响。最近，越来越多的研究从天然产物中寻找新的治疗剂，其中植物衍生的生物活性化合物越来越受到研究。柚皮苷（NG）和它的苷元柚皮素（NGE）大量存在于葡萄柚和橙子等柑橘类水果中。它们的抗癌活性被认为是通过几种细胞信号转导途径发挥作用的。最近，不同的药理学策略基于联合治疗，涉及 NG 和 NGE 与当前的抗癌药物相比，与单药治疗相比，显示出巨大的协同作用。此外，NG 和 NGE 已被报道可以克服多药耐药性，这是临床治疗的主要障碍之一，这是由于癌症中的不同防御机制引起的。因此，我们全面综述了 NG 和 NGE 通过不同的信号转导途径对几种类型的癌症的抑制作用、与当前抗癌药物联合使用的作用以及癌症联合治疗的疗效。
