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Research article
Zengxin Qi
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5206-9948
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Background: Autophagy is considered to beanother 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. Results: In the present research, we report that melatonin or its agonist, agomelatine, induced autophagy inA172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, whichwas 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. Conclusions: These 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.
Keywords
Melatonin; agomelatine; autophagy; apoptosis; glioma
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CURRENT STATUS: Published
View the published article at BMC Neuroscience.
No community comments so far
Editorial decision: Accept
On 13 Dec, 2019
Editor assigned
On 12 Dec, 2019
Reviewers invited
Invitations sent on 12 Dec, 2019
Reviewer #1 agreed
On 12 Dec, 2019
Review #1 received
Received 12 Dec, 2019
Submission checks complete
On 11 Dec, 2019
Editor invited
On 11 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 08 Dec, 2019
Review #1 received
Received 06 Dec, 2019
Review #2 received
Received 29 Nov, 2019
Reviewer #2 agreed
On 29 Nov, 2019
Reviewer #1 agreed
On 26 Nov, 2019
Editor assigned
On 24 Nov, 2019
Reviewers invited
Invitations sent on 24 Nov, 2019
Submission checks complete
On 23 Nov, 2019
Editor invited
On 23 Nov, 2019
Version 2
Posted 17 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 12 Nov, 2019
Review #1 received
Received 11 Nov, 2019
Reviewer #2 agreed
On 30 Oct, 2019
Review #2 received
Received 30 Oct, 2019
Reviewer #1 agreed
On 28 Oct, 2019
Reviewers invited
Invitations sent on 27 Oct, 2019
Editor assigned
On 15 Oct, 2019
Submission checks complete
On 14 Oct, 2019
Editor invited
On 14 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 15 Sep, 2019
Review #2 received
Received 13 Sep, 2019
Review #1 received
Received 10 Sep, 2019
Reviewer #2 agreed
On 04 Sep, 2019
Editor assigned
On 27 Aug, 2019
Reviewers invited
Invitations sent on 27 Aug, 2019
Reviewer #1 agreed
On 27 Aug, 2019
Submission checks complete
On 26 Aug, 2019
Editor invited
On 26 Aug, 2019
First submitted
On 13 Aug, 2019
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PDF Downloads: ...
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Subject Areas
Developmental Neuroscience
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A new preprint design is coming!
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See the published version of this preprint at BMC Neuroscience.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Zengxin Qi
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5206-9948
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Neuroscience.
No community comments so far
Editorial decision: Accept
On 13 Dec, 2019
Editor assigned
On 12 Dec, 2019
Reviewers invited
Invitations sent on 12 Dec, 2019
Reviewer #1 agreed
On 12 Dec, 2019
Review #1 received
Received 12 Dec, 2019
Submission checks complete
On 11 Dec, 2019
Editor invited
On 11 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 08 Dec, 2019
Review #1 received
Received 06 Dec, 2019
Review #2 received
Received 29 Nov, 2019
Reviewer #2 agreed
On 29 Nov, 2019
Reviewer #1 agreed
On 26 Nov, 2019
Editor assigned
On 24 Nov, 2019
Reviewers invited
Invitations sent on 24 Nov, 2019
Submission checks complete
On 23 Nov, 2019
Editor invited
On 23 Nov, 2019
Version 2
Posted 17 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 12 Nov, 2019
Review #1 received
Received 11 Nov, 2019
Reviewer #2 agreed
On 30 Oct, 2019
Review #2 received
Received 30 Oct, 2019
Reviewer #1 agreed
On 28 Oct, 2019
Reviewers invited
Invitations sent on 27 Oct, 2019
Editor assigned
On 15 Oct, 2019
Submission checks complete
On 14 Oct, 2019
Editor invited
On 14 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 15 Sep, 2019
Review #2 received
Received 13 Sep, 2019
Review #1 received
Received 10 Sep, 2019
Reviewer #2 agreed
On 04 Sep, 2019
Editor assigned
On 27 Aug, 2019
Reviewers invited
Invitations sent on 27 Aug, 2019
Reviewer #1 agreed
On 27 Aug, 2019
Submission checks complete
On 26 Aug, 2019
Editor invited
On 26 Aug, 2019
First submitted
On 13 Aug, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Developmental Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Neuroscience.
Background: Autophagy is considered to beanother 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. Results: In the present research, we report that melatonin or its agonist, agomelatine, induced autophagy inA172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, whichwas 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. Conclusions: These 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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