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

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Curcumin derivatives like MTH-3 offer enhanced solubility for therapeutic applications.
• Oral squamous cell carcinoma (OSCC) often develops resistance to standard chemotherapy, necessitating novel treatment strategies.

Purpose of the Study:

• To investigate the anticancer mechanisms of MTH-3 on cisplatin-resistant human oral cancer cells (CAL27 CAR).
• To elucidate the role of MTH-3 in inducing cell death pathways and autophagy in resistant oral cancer models.

Main Methods:

• Cell viability assays were performed to assess MTH-3's effect on CAR cell proliferation.
• Flow cytometry and staining were utilized to analyze cell cycle and apoptosis.
• Western blot analysis was employed to examine the expression of key proteins involved in autophagy and apoptosis.
• Caspase activity assays and mitochondrial membrane potential measurements were conducted.

Main Results:

• MTH-3 significantly reduced the viability of CAL27 CAR cells.
• MTH-3 treatment markedly induced autophagy and upregulated autophagy-related proteins.
• Transcription Factor EB (TFEB) was identified as a potential molecular target of MTH-3.
• MTH-3 triggered the intrinsic apoptotic pathway, evidenced by increased caspase-3 and caspase-9 activities and decreased mitochondrial membrane potential.

Conclusions:

• MTH-3 effectively induces both autophagy and apoptosis in cisplatin-resistant oral cancer cells.
• The observed effects are mediated, at least in part, through the TFEB pathway.
• MTH-3 demonstrates potential as a novel pharmacological agent for overcoming chemoresistance in oral cancer.