Dysregulated cell-cycle progression is a central driver of breast cancer proliferation and is largely orchestrated by cyclin-dependent kinases (CDKs) and their regulatory cyclins. Although Cyclo(Pro-Tyr), a bioactive cyclic dipeptide, has been previously reported to induce apoptosis, its involvement in cell-cycle regulation and proliferative signaling remains insufficiently explored. Given that aberrant CDK activity is a hallmark of breast cancer, the present study investigated the interaction of Cyclo(Pro-Tyr) with key cell-cycle regulatory proteins using molecular docking and evaluated its anti-proliferative potential in breast cancer cells. Molecular docking was carried out using AutoDockTools against CDK2, CDK4, CDK6, and Cyclin D1, which collectively regulate G1–S phase transition. Cyclo(Pro-Tyr) demonstrated suitable binding affinities across all targets and formed stable interactions within functionally relevant regions of the proteins. Interaction analyses indicated a predominantly non-ATP-competitive binding mode, suggesting possible modulation of CDK–cyclin regulatory interfaces rather than direct enzymatic inhibition. Experimental validation using an MTT assay revealed a concentration-dependent reduction in MCF-7 breast cancer cell viability following 24 hours exposure, with an IC₅₀ value consistent with suppression of proliferative capacity. Collectively, these findings suggest that Cyclo(Pro-Tyr) may exert anti-proliferative effects through modulation of CDK-driven cell-cycle regulation. This study supported computational evidence linking CDK–cyclin interaction with growth suppression and supports the further exploration of Cyclo(Pro-Tyr) as a multi-target peptide-based candidate for breast cancer therapy.
Balachandran et al. (Tue,) studied this question.