Cited by 277Metabolism, Diabetes, and CancerCancer, Hypoxia, and MetabolismPI3K/AKT/mTOR signaling in cancer

Metformin as an Anticancer Agent

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Vancura, Ales, Bu, Pengli, Bhagwat, Madhura, Zeng, Joey, Vancurova, Ivana·2018·Trends in Pharmacological Sciences

Abstract

Metformin has been a frontline therapy for type 2 diabetes (T2D) for many years. Its effectiveness in T2D treatment is mostly attributed to its suppression of hepatic gluconeogenesis; however, the mechanistic aspects of metformin action remain elusive. In addition to its glucose-lowering effect, metformin possesses other pleiotropic health-promoting effects that include reduced cancer risk and tumorigenesis. Metformin inhibits the electron transport chain (ETC) and ATP synthesis; however, recent data reveal that metformin regulates AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) by multiple, mutually nonexclusive mechanisms that do not necessarily depend on the inhibition of ETC and the cellular ATP level. In this review, we discuss recent advances in elucidating the molecular mechanisms that are relevant for metformin use in cancer treatment.

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  1. [20]Miller RA (2013) Biguanides suppress hepatic glucagon signaling by decreasing production of cyclic AMP. Nature 494, 256– 260 23292513 PMC3573218

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Authors
Vancura, A., Bu, P., Bhagwat, M., Zeng, J., & Vancurova, I.
Affiliations
St. John's University (US)
Venue
Trends in Pharmacological Sciences
Publisher
Elsevier BV
Published
2018-10
Volume
39
Issue
10
Pages
867-878
ISSN
0165-6147 (ISSN-L)
OpenAlex
W2888538492
Cited by
274
References
107
Citations by year
2026: 14 · 2025: 29 · 2024: 34 · 2023: 40 · 2022: 47 · 2021: 39 · 2020: 41 · 2019: 30
FWCI
2.69
Type
journal article
Language
en
Open access
Locations
  • Trends in Pharmacological Sciences (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (GM120710)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
metformin, anticancer effects, type 2 diabetes, AMPK, mTORC1, electron transport inhibition, ATP production, hepatic gluconeogenesis, cancer risk reduction, carcinogenesis, pleiotropy
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Animals, Antineoplastic Agents, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Electron Transport Complex I, AMP-Activated Protein Kinases

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