Exploring the Role of Neoflavonoids in Inducing Cell Cycle Arrest in Cancer Cells: In Silico study

Neoflavonoids Inducing Cell Cycle Arrest in Cancer Cells

Abstract

Background: Cancer remains a major global health problem, with 20 million newly diagnosed cases and an estimated 9.7 million cancer deaths in 2022. Cancer cell proliferation is closely related to the dysregulation of cell cycle progression, which is mainly mediated by cyclin-dependent kinases (CDKs). In this study, neoflavonoids are investigated as novel therapeutic agents that target CDK4, a key regulator of cell cycle transition from G1 to S phase. Method: We performed a pan-cancer analysis of CDK expression using several state-of-the-art databases and found high CDK4 levels in many cancers, and in several cancers higher CDK4 levels were associated with poorer patient survival. Molecular docking studies were performed on 26 neoflavonoid compounds to determine their binding affinity at the ATP binding site of CDK4 to the known inhibitors aemaciclib and flavopiridol. Results: We found that several neoflavonoids bind with similar affinities to these established inhibitors and thus may be effective CDK4 inhibitors. Conclusion: This research shows the therapeutic potential of neoflavonoids in the treatment of cancer and suggests that more preclinical studies are needed to confirm their effectiveness and clarify their mechanisms of action.