Cytotoxic Activity of Epetraborole Against Cancer Cell Lines

Objective: Antibiotic repurposing represents a promising strategy in oncology, utilizing well-characterized pharmacophores to exploit conserved vulnerabilities in cancer cells. This study aimed to evaluate the cytotoxic potential of epetraborole (EP), a benzoxaborole-class leucyl-tRNA synthetase inhibitor, against various cancer cell types. Methods: The cytotoxic effects of EP were assessed in five cancer cell lines: malignant mesothelioma (CARM-L12 TG3), osteosarcoma (MG63), and colorectal carcinomas (HT-29, SW-48, and 2A3). MTT cell viability assays were conducted to determine dose- and time-dependent responses following 72-hour exposure. Antibacterial activity was verified by determining the minimum inhibitory concentration (MIC) against Escherichia coli. Results: EP exhibited significant cytotoxic activity in a dose- and time-dependent manner. The compound showed highest potency against CARM-L12 TG3 (IC50= 0.408 ± 1.1 µg/mL) and MG63 (IC₅₀ = 0.875 ± 1.6 µg/mL) cell lines, while colorectal carcinoma cells were less sensitive (IC50 > 3 µg/mL). Antibacterial testing confirmed EP’s bioactivity, with an MIC value of 0.5 μg/mL against E. coli. Conclusion: Epetraborole demonstrates strong cytotoxic potential, particularly against mesenchymal-derived cancers such as mesothelioma and osteosarcoma. These results suggest that EP is a promising candidate for repurposing in oncology, targeting malignancies dependent on protein synthesis machinery.