Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential

<jats:p>Dinaciclib, a potent cyclin-dependent kinase (CDK) inhibitor, has demonstrated considerable antitumor effects in various malignancies. However, its impact on oral squamous cell carcinoma (OSCC), a predominant and highly aggressive form of head and neck squamous cell carcinoma (HNSC) with limited treatment options, remains underexplored. We conducted gene set enrichment analyses in HNSC patients that reinforced the relevance of these cell cycle-related genes to OSCC pathogenesis. Given the known dysregulation of cell cycle-related genes in HNSC patients, we hypothesized that Dinaciclib may inhibit OSCC growth by targeting overexpressed cyclins and CDKs, thereby disrupting cell cycle progression and inducing apoptosis. This study investigated Dinaciclib’s effects on cell proliferation, cell cycle progression, and apoptosis in the OSCC cell lines Ca9-22, OECM-1, and HSC-3. Our results demonstrated that Dinaciclib significantly reduces OSCC cell proliferation in a dose-dependent manner. Flow cytometry and Western blot analyses showed that Dinaciclib induces cell cycle arrest at the G1/S and G2/M transitions by downregulating Cyclins A, B, D, and E, along with CDKs 1 and 2—key regulators of these checkpoints. Furthermore, Dinaciclib treatment upregulated apoptotic markers, such as cleaved-caspase-3 and cleaved-PARP, confirming its pro-apoptotic effects. In conclusion, these findings highlight Dinaciclib’s therapeutic promise in OSCC by simultaneously disrupting cell cycle progression and inducing apoptosis. These results support further exploration of Dinaciclib as a viable monotherapy or combination treatment in OSCC and other HNSC subtypes to improve patient outcomes.</jats:p>