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Molecular targets of metformin antitumor action

Stanisław Sośnicki1, Małgorzata Kapral1, Ludmiła Węglarz1

  • 1School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biochemistry, Sosnowiec, Poland.

Pharmacological Reports : PR
|July 1, 2016
PubMed

Insights

Metformin, a diabetes drug, may fight cancer by lowering cell energy and impacting key growth pathways like AMPK and mTOR. This review explores its anticancer mechanisms and signaling pathways.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Metformin is a primary treatment for diabetes mellitus.
  • Epidemiological studies suggest metformin use is linked to reduced risks of various cancers.
  • Preclinical research indicates potential anticancer mechanisms for metformin.

Purpose of the Study:

  • To review the mechanisms underlying metformin's antitumor activity.
  • To focus on the drug's impact on insulin/PI3K/mTOR and AMP-activated kinase (AMPK) signaling pathways.
  • To discuss factors influencing metformin's novel anticancer effects.

Main Methods:

  • Literature review of epidemiological and preclinical studies.
  • Analysis of metformin's effects on cellular energy status and metabolic signaling.
  • Examination of metformin's influence on key cancer-related pathways like mTOR and AMPK.

Main Results:

  • Metformin decreases cellular energy status, activating AMP-activated kinase (AMPK).
  • This activation leads to reduced serum insulin and insulin-like growth factor I (IGF-I) levels.
  • Metformin directly inhibits cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes.

Conclusions:

  • Metformin exhibits anticancer properties through both indirect (metabolic) and direct (signaling pathway) mechanisms.
  • Its impact on AMPK and mTOR pathways is crucial for its antineoplastic effects.
  • Further research into factors modulating metformin's anticancer activity is warranted.
Keywords:
Antitumor propertiesMetforminMolecular mechanisms

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