A Narrative Review on Therapeutic Potential of Naringenin in Colorectal Cancer: Focusing on molecular and biochemical processes

Abstract

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, anti-cancer, 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, Cdk7) and anti-apoptotic genes (Bcl2, x-IAP, 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.