This preprint is under consideration at Medical Oncology. A preprint is 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.
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Research Article
Qi-Yang He
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medicinal Biotechnology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3694-6036
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This work is licensed under a CC BY 4.0 License. Read Full License
Boningmycin (BON), a new member of the bleomycin family, exhibits highly potent activity against tumor cells in vitro and in vivo. It remains unclear if BON can affect the protein levels of programmed death ligand-1 (PD-L1) in a manner similar to that of other antitumor agents. Potent inhibition of cell survival by BON was observed in non-small-cell lung cancer NCI-H460 cells and sarcoma HT1080 cells. Apoptosis-independent reduction of PD-L1 was observed after exposure to BON. Furthermore, BON-treatment increased AMP-activated protein kinase phosphorylation, however, this increase was suppressed by treatment with specific inhibitor (compound C) or RNAi-mediated knockdown of AMPKα. BON-induced PD-L1 reduction is mediated by the endoplasmic reticulum-associated degradation pathway. Its mode of action is similar to that of metformin on the PD-L1 protein. In conclusion, it is firstly reported that BON can decrease PD-L1 protein levels through the AMPK activated endoplasmic reticulum- associated degradation pathway.
Keywords
boningmycin, PD-L1, apoptosis, AMP-activated protein kinase, endoplasmic reticulum-associated degradation pathway
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Received 31 Oct, 2021
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This preprint is under consideration at Medical Oncology. A preprint is 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
Qi-Yang He
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medicinal Biotechnology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3694-6036
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: Under Review
Version 1
Posted 29 Oct, 2021
No community comments so far
Reviews received
Received 31 Oct, 2021
Reviewers invited
Invitations sent on 27 Oct, 2021
Editor assigned
On 26 Oct, 2021
First submitted
On 25 Oct, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Oncology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Boningmycin (BON), a new member of the bleomycin family, exhibits highly potent activity against tumor cells in vitro and in vivo. It remains unclear if BON can affect the protein levels of programmed death ligand-1 (PD-L1) in a manner similar to that of other antitumor agents. Potent inhibition of cell survival by BON was observed in non-small-cell lung cancer NCI-H460 cells and sarcoma HT1080 cells. Apoptosis-independent reduction of PD-L1 was observed after exposure to BON. Furthermore, BON-treatment increased AMP-activated protein kinase phosphorylation, however, this increase was suppressed by treatment with specific inhibitor (compound C) or RNAi-mediated knockdown of AMPKα. BON-induced PD-L1 reduction is mediated by the endoplasmic reticulum-associated degradation pathway. Its mode of action is similar to that of metformin on the PD-L1 protein. In conclusion, it is firstly reported that BON can decrease PD-L1 protein levels through the AMPK activated endoplasmic reticulum- associated degradation pathway.
Figure 1
Figure 2
Figure 3
Figure 4
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