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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. Significance statement: The review discusses the molecular and biochemical processes related to naringenin (NAR's) effects on colorectal cancer (CRC), emphasizing its diverse pharmacological and biological properties. NAR interacts with estrogen receptors, regulates gene expression related to the p53 signaling pathway, promotes apoptosis, inhibits enzymes involved in cell survival and proliferation, decreases cyclin D1 levels, and reduces the expression of cyclin‐dependent kinases and antiapoptotic genes in CRC cells. In vitro studies demonstrate that NAR derivatives have better inhibitory activities on CDK2 than NAR, suggesting their potential as therapeutic agents for CRC. [ABSTRACT FROM AUTHOR]

In recent decades, in many countries of the world there has been an increase in the incidence of colorectal cancer (CRC). The annual occurrence of 50 new cases of colorectal cancer per 100,000 population determines a 5% population risk of developing the disease throughout life 1. An alarming fact is that for the 100 newly diagnosed patients with CRC, more than 70 deaths occur, of which, in the 1st year from the moment of diagnosis, about 40%. This circumstance is due to the fact that when patients first go to the doctor, advanced forms of CRC (stage III-IV) are diagnosed in 62.4% of patients. In 25-30% of patients, distant metastases are detected at the time of surgery. In recent years, there has been a tendency to expand indications for organ-preserving operations in the CRC.At the same time, it is necessary to formulate clear criteria for their implementation on the basis of a comparative analysis of long-term treatment results, the frequency of local regional relapses, the development and implementation of techniques using staplers, as well as the justification of indications for the use of combined and complex treatment programs that increase the radicalism and ablasticity of surgical interventions. [ABSTRACT FROM AUTHOR]