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Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1

Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-met...

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Autores principales: Chen, Yiyan, Li, Min, Yang, Yanying, Lu, Yan, Li, Xiaoying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723917/
https://www.ncbi.nlm.nih.gov/pubmed/36356901
http://dx.doi.org/10.1016/j.jbc.2022.102678
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author Chen, Yiyan
Li, Min
Yang, Yanying
Lu, Yan
Li, Xiaoying
author_facet Chen, Yiyan
Li, Min
Yang, Yanying
Lu, Yan
Li, Xiaoying
author_sort Chen, Yiyan
collection PubMed
description Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor nuclear factor E2–related factor 2. In addition, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the nuclear factor E2–related factor 2–HMGCS1 axis, which might be a potential target in cancer prevention and treatment.
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spelling pubmed-97239172022-12-07 Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1 Chen, Yiyan Li, Min Yang, Yanying Lu, Yan Li, Xiaoying J Biol Chem Research Article Metformin, an antidiabetic drug, shows some potent antitumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here, we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor nuclear factor E2–related factor 2. In addition, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the nuclear factor E2–related factor 2–HMGCS1 axis, which might be a potential target in cancer prevention and treatment. American Society for Biochemistry and Molecular Biology 2022-11-08 /pmc/articles/PMC9723917/ /pubmed/36356901 http://dx.doi.org/10.1016/j.jbc.2022.102678 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Chen, Yiyan
Li, Min
Yang, Yanying
Lu, Yan
Li, Xiaoying
Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title_full Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title_fullStr Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title_full_unstemmed Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title_short Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1
title_sort antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme hmgcs1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723917/
https://www.ncbi.nlm.nih.gov/pubmed/36356901
http://dx.doi.org/10.1016/j.jbc.2022.102678
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