Melatonin suppresses TPA-induced metastasis in nasopharyngeal carcinoma. - GreenMedInfo Summary
Melatonin suppresses TPA-induced metastasis by downregulating matrix metalloproteinase-9 expression through JNK/SP-1 signaling in nasopharyngeal carcinoma.
J Pineal Res. 2016 Sep 7. Epub 2016 Sep 7. PMID: 27600920
Nasopharyngeal carcinoma (NPC), a disease common in the South-East Asian population, has high lymph node metastatic ability. Melatonin, an endogenously produced substance present in animals, plants, fungi, and bacteria, has oncotstatic activity via several mechanisms. The molecular mechanisms involved in melatonin-mediated tumor inhibitory potential are not completely defined. Here, we show that melatonin treatment inhibits TPA-induced cell motility by regulating matrix metalloproteinase-9 (MMP-9) expression in NPC. We also identified the signaling cascade through which melatonin inhibits MMP-9 expression; this involves melatonin regulating the binding activity of the transcription factor specificity protein-1 (SP-1)-DNA. Our mechanistic analysis further reveals that the c-Jun N terminal kinase/mitogen-activate protein kinase pathway is involved in the melatonin-mediated tumor suppressor activity. Furthermore, the findings indicate a functional link between melatonin-mediated MMP-9 regulation and tumor suppressing ability and provide new insights into the role of melatonin-induced molecular and epigenetic regulation of tumor growth. Thus, we conclude that melatonin suppresses the motility of NPC by regulating TPA-induced MMP-9 gene expression via inhibiting SP-1-DNA binding ability. The results provide a functional link between melatonin-mediated SP-1 regulation and the anti-metastatic actions of melatonin on nasopharyngeal carcinoma. This article is protected by copyright. All rights reserved.