MTH-3 sensitizes oral cancer cells to cisplatin via regulating TFEB

Abstract Objectives MTH-3, a curcumin derivative, exhibits improved water solubility. This study aims to elucidate the mechanisms underlying the anticancer effects of MTH-3 on human oral squamous cell carcinoma CAL27 cisplatin-resistant (CAR) cells. Methods To evaluate the biological functions of MTH-3 in CAR cells, flow cytometry, staining, and western blot analyses were used. Key findings MTH-3 reduced CAR cell viability and significantly induced autophagy in the presence of 10 and 20 μM MTH-3. Transcription factor EB was identified as the potential target of MTH-3. Autophagy-related proteins were upregulated after 24 h of MTH-3 incubation. MTH-3 treatment increased caspase-3 and caspase-9 enzyme activities. Mitochondrial membrane potential was decreased after MTH-3 treatment. MTH-3 triggered the intrinsic apoptotic pathway. Conclusions MTH-3 induces autophagy and apoptosis of CAR cells via TFEB. MTH-3 might be an effective pharmacological agent for treating oral cancer cells.