Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin | increase | apoptosis | TSCC cell line Cal27 | significant | induced significant apoptosis | #1 |
melatonin | increase | autophagic flux | Cal27 cells | - | induced autophagic flux | #2 |
melatonin | increase | GFP-LC3 puncta formation | Cal27 cells | - | formation of GFP-LC3 puncta | #3 |
melatonin | increase | LC3-II levels | Cal27 cells | - | upregulation of LC3-II | #4 |
melatonin | decrease | SQSTM1/P62 levels | Cal27 cells | - | downregulation of SQSTM1/P62 | #5 |
pharmacological or genetic blockage of autophagy | increase | melatonin-induced apoptosis | melatonin-treated Cal27 cells | - | enhanced melatonin-induced apoptosis | #6 |
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anticarcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62. Moreover, pharmacological or genetic blockage of autophagy enhanced melatonin-induced apoptosis, indicating a cytoprotective role of autophagy in melatonin-treated Cal27 cells. Mechanistically, melatonin induced TFE3