title: Molecular targets of metformin antitumor action.
abstract: Epidemiological studies have shown that metformin, a first line therapeutic agent for diabetes mellitus, reduced the risk of developing various malignancies. Several preclinical studies established some possible mechanisms of its anticancer effects. The primary effect of metformin action is a decrease in cell energy status, which activates AMP-activated kinase (AMPK), a cellular metabolic sensor. This event is followed by a decrease in serum concentrations of insulin and insulin growth factor I (IGF-I), the potent mitogens for cancer cells. In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes. This review gathers information on mechanisms of metformin antitumor activity, with special attention given to the impact of this antidiabetic drug on insulin/PI3K/mTOR and AMPK signaling. Furthermore, the factors required for this novel activity of metformin are discussed.
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biochemistry, Sosnowiec, Poland. Electronic address: ssosnicki88@gmail.com.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Sośnicki
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biochemistry, Sosnowiec, Poland. Electronic address: mkapral@sum.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kapral
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biochemistry, Sosnowiec, Poland. Electronic address: lweglarz@sum.edu.pl.
authors.forename: Ludmiła
authors.initials: L
authors.lastname: Węglarz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Antitumor properties; Metformin; Molecular mechanisms