1. Academic Validation
  2. Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma

Melatonin triggers autophagic cell death by regulating RORC in Hodgkin lymphoma

  • Biomed Pharmacother. 2020 Mar;123:109811. doi: 10.1016/j.biopha.2020.109811.
Gege Yan 1 Hong Lei 1 Mingyu He 1 Rui Gong 1 Yang Wang 1 Xiaoqi He 1 Guanghui Li 1 Ping Pang 1 Xin Li 1 Shuting Yu 1 Weijie Du 2 Ye Yuan 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China; Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150086, China.
  • 2 Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150086, China. Electronic address: adugo@163.com.
  • 3 Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China; Department of Clinical Pharmarcology, College of Pharmacy, Harbin Medical University, Harbin 150086, China. Electronic address: yuanye_hmu@126.com.
Abstract

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.

Keywords

Autophagy; Hodgkin lymphoma (HL); Melatonin (Mel); Retinoic acid-related orphan receptors (RORs).

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