Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Cell Biochem Funct. 2024 Apr;42(3):e4011. doi: 10.1002/cbf.4011.
Colorectal cancer (CRC) is a common and highly metastatic cancer affecting people worldwide. Drug resistance and unwanted side effects are some of the limitations of current treatments for CRC. Naringenin (NAR) is a naturally occurring compound found in abundance in various citrus fruits such as oranges, grapefruits, and tomatoes. It possesses a diverse range of pharmacological and biological properties that are beneficial for human health. Numerous studies have highlighted its antioxidant, anticancer, and anti-inflammatory activities, making it a subject of interest in scientific research. This review provides a comprehensive overview of the effects of NAR on CRC. The study's findings indicated that NAR: (1) interacts with estrogen receptors, (2) regulates the expression of genes related to the p53 signaling pathway, (3) promotes apoptosis by increasing the expression of proapoptotic genes (Bax, caspase9, and p53) and downregulation of the antiapoptotic gene Bcl2, (4) inhibits the activity of enzymes involved in cell survival and proliferation, (5) decreases cyclin D1 levels, (6) reduces the expression of cyclin-dependent kinases (Cdk4, Cdk6, and Cdk7) and antiapoptotic genes (Bcl2, x-IAP, and c-IAP-2) in CRC cells. In vitro CDK2 binding assay was also performed, showing that the NAR derivatives had better inhibitory activities on CDK2 than NAR. Based on the findings of this study, NAR is a potential therapeutic agent for CRC. Additional pharmacology and pharmacokinetics studies are required to fully elucidate the mechanisms of action of NAR and establish the most suitable dose for subsequent clinical investigations.
结直肠癌(CRC)是一种常见且高度转移性的癌症,影响着全球的人们。耐药性和不良反应是目前 CRC 治疗的一些局限性。柚皮素(NAR)是一种天然存在的化合物,在橙子、葡萄柚和西红柿等各种柑橘类水果中含量丰富。它具有多种药理和生物学特性,对人类健康有益。许多研究强调了它的抗氧化、抗癌和抗炎活性,使其成为科学研究的一个关注点。这篇综述全面概述了 NAR 对 CRC 的影响。研究结果表明,NAR:(1)与雌激素受体相互作用,(2)调节与 p53 信号通路相关的基因表达,(3)通过增加促凋亡基因(Bax、caspase9 和 p53)的表达和下调抗凋亡基因 Bcl2 来促进细胞凋亡,(4)抑制参与细胞存活和增殖的酶的活性,(5)降低细胞周期蛋白 D1 水平,(6)降低 CRC 细胞中细胞周期蛋白依赖性激酶(Cdk4、Cdk6 和 Cdk7)和抗凋亡基因(Bcl2、x-IAP 和 c-IAP-2)的表达。还进行了体外 CDK2 结合测定,表明 NAR 衍生物对 CDK2 的抑制活性优于 NAR。基于这项研究的结果,NAR 是 CRC 的一种潜在治疗剂。需要进行更多的药理学和药代动力学研究,以充分阐明 NAR 的作用机制,并确定后续临床研究最合适的剂量。