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

J Pharm Pharmacol. 2022 Sep 1;74(9):1261-1273. doi: 10.1093/jpp/rgac056.

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.

Keywords: MTH-3; apoptosis; autophagy; oral squamous cell carcinoma (OSCC); transcription factor EB (TFEB).

MeSH terms

  • Apoptosis
  • Autophagy
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / pharmacology
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Humans
  • Mouth Neoplasms* / pathology

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFEB protein, human
  • Cisplatin