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Inhibition of autophagy triggers melatonin-induced apoptosis in glioblastoma cells

Authors
  • Zhou, Nan1
  • Wei, Zi Xuan1
  • Qi, Zeng Xin1
  • 1 Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China , Shanghai (China)
Type
Published Article
Journal
BMC Neuroscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 23, 2019
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12868-019-0545-1
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundAutophagy is considered to be another restorative focus for the treatment of brain tumors. Although several research have demonstrated that melatonin induces autophagy in colon cancer and hepatoma cells, there has not been any direct evidence of whether melatonin is capable of inducing autophagy in human glioma cells.ResultsIn the present research, we report that melatonin or its agonist, agomelatine, induced autophagy in A172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, which was significantly attenuated by treatment with luzindole, a melatonin receptor antagonist. Furthermore, by suppressing autophagy at the late-stage with bafilomycin A1 and early stage with 3-MA, we found that the melatonin-induced autophagy was activated early, and the autophagic flux was complete. Melatonin treatment alone did not induce any apoptotic changes in the glioblastoma cells, as measured by flow cytometry. Western blot studies confirmed that melatonin alone prominently upregulated the levels of Beclin 1 and LC3 II, which was accompanied by an increase in the expression of Bcl-2, whereas it had no effect on the expression of Bax in the glioblastoma cells. Remarkably, co-treatment with 3-MA and melatonin significantly enhanced the apoptotic cell population in the glioblastoma cells, along with a prominent decrease in the expression of bcl-2 and increase in the Bax expression levels, which collectively indicated that the disruption of autophagy triggers the melatonin-induced apoptosis in glioblastoma cells.ConclusionsThese results provide information indicating that melatonin may act as a common upstream signal between autophagy and apoptosis, which may lead to the development of new therapeutic strategies for glioma.

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