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.