Delafloxacin suppresses DEPDC1 expression and induces G2/M arrest in non‐small cell lung cancer cells: A drug repurposing study
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract 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 ICof 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. This study presents D
Abstract
Abstract 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 ICof 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. This study presents Delafloxacin repurposed as a DEPDC1‐targeting therapeutic aiming to suppress lung cancer progression. It highlights a novel strategy for lung cancer treatment with potential clinical applications. graphical