Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Melatonin (Mel) | decrease | Hodgkin lymphoma (HL) | HL cells | - | exerted anti-tumor activities | #1 |
Melatonin (Mel) | decrease | cell proliferation | HL cells | - | inhibiting | #2 |
Melatonin (Mel) | increase | cell apoptosis | HL cells | - | promoting | #3 |
Melatonin (Mel) treatment | increase | expression of LC3-II | HL cells | - | increased | #4 |
Melatonin (Mel) treatment | decrease | p62 proteins | HL cells | - | decreased | #5 |
Melatonin (Mel) treatment | increase | production of autolysosome | HL cells | - | enhanced | #6 |
Melatonin (Mel) treatment | increase | autophagy | HL cells | - | induced activation of | #7 |
Melatonin (Mel) treatment together with autophagy inhibitors 3-MA or CQ | increase | damage effect of Mel | HL cells | - | exacerbated | #8 |
Melatonin (Mel) treatment | increase | expression of G protein-coupled receptors MT2 | HL cells | - | increased | #9 |
Melatonin (Mel) treatment | increase | expression of retinoic acid-related orphan receptors (RORs) | HL cells | - | increased | #10 |
Melatonin (Mel) treatment | increase | RORC | HL cells | - | has the highest increase | #11 |
RORC overexpression | increase | autophagy activation | HL cells | - | induced | #12 |
Melatonin (Mel) | decrease | HL | HL cells | - | showed tumor-suppressive role | #13 |
Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.