Delafloxacin suppresses DEPDC1 expression and induces G2/M arrest in non-small cell lung cancer cells: A drug repurposing study.

Emerging evidence highlights the oncogenic role of the Dishevelled, Egl-10, and Pleckstrin domains containing 1 (DEPDC1) gene in lung cancer progression, making it an attractive therapeutic target. In this study, we investigated the anti-cancer potential of Delafloxacin, a fluoroquinolone antibiotic, in DEPDC1-overexpressing non-small cell lung cancer, NCI-H1299 cells. In silico docking of 1399 FDA-approved compounds using AutoDock Vina confirmed the strong binding affinity of Delafloxacin to the DEPDC1 active site (binding energy -7.1 kcal/mol). Delafloxacin treatment resulted in dose-dependent suppression of cell proliferation, with an IC50 of approximately 30 μg/mL. RT-qPCR revealed significant downregulation of DEPDC1 and several key regulators of proliferation (RAS, EGFR), mitotic progression (Cyclin-dependent kinase 1 (CDK1), CCNB2, KIF2C), and survival (BIRC5). Cell cycle analysis demonstrated G2/M phase accumulation upon Delafloxacin treatment, consistent with transcriptional repression of CDK1 and CCNB2. In vivo, Delafloxacin administration (15 mg/kg) significantly reduced tumor growth in a xenograft mouse model without overt toxicity. While these findings identify Delafloxacin as a candidate for repurposing in lung cancer, the observed downregulation of DEPDC1 represents a correlative finding rather than validated direct targeting. This study provides a rationale for further investigation of Delafloxacin in DEPDC1-associated malignancies.