Maslinic Acid as a Candidate Small-Molecule CDK4 Inhibitor for Lung Cancer

Background

Lung cancer is a significant cause of cancer-related death, emphasizing the need for current targeted therapies. CDK4, an imperative regulator of cell-cycle progression and the G1/S transition, is a promising anticancer target. So, maslinic acid, a candidate small-molecule CDK4 inhibitor for lung cancer, was studied using integrated in silico and in vitro approaches.

Purpose

To evaluate maslinic acid as a potential small-molecule CDK4 inhibitor and assess its anticancer activity in A549 lung carcinoma cells.

Methods and Materials

Sequence-based domain analyses confirmed conserved protein kinase features, with an ATP-binding region and catalytic residues. PPI and GO enrichment analyses defined the biological role of CDK4. Molecular docking observed maslinic acid binding within the CDK4 active pocket. Cell viability assays, along with CDK4 mRNA and protein level analyses, were performed in A549 cells.

Results

The target protein presented a conserved protein kinase/PK-like domain with crucial functional motifs. CDK4 was enriched in pathways related to cell-cycle regulation, cyclin-dependent kinase activity, and G1/S transition. Docking revealed stable binding of maslinic acid within the CDK4 pocket, involving van der Waals, alkyl, and Pi-alkyl interactions with residues including PHE124, LEU141, LYS142, ASP140, ILE146, SER199, VAL200, and MET197. In vitro, maslinic acid reduced A549 cell viability in both dose-dependent and time-dependent manners and significantly decreased CDK4 mRNA expression and protein levels.

Conclusion

Maslinic acid shows potential as a candidate small-molecule CDK4 inhibitor for lung cancer. Its favorable CDK4 binding, association with cell-cycle pathways, and inhibitory effects on cell viability and CDK4 expression support further development as a potential therapeutic lead.