title: Metformin, cancer and glucose metabolism.
abstract: Metformin is the first-line treatment for type 2 diabetes. Results from several clinical studies have indicated that type 2 diabetic patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once it has entered the cell through organic cation transporters, metformin decreases mitochondrial respiration chain activity and ATP production that, in turn, activates AMP-activated protein kinase, which regulates energy homeostasis. In addition, metformin reduces cellular energy availability and glucose entrapment by inhibiting hexokinase-II, which catalyses the glucose phosphorylation reaction. In this review, we discuss recent findings on molecular mechanisms that sustain the anticancer effect of metformin through regulation of glucose metabolism. In particular, we have focused on the emerging action of metformin on glycolysis in normal and cancer cells, with a drug discovery perspective.
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salani
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Cordera
authors.affiliation: Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy Department of Internal Medicine (DIMI)University of Genova, Viale Benedetto XV/6, 16132 Genova, ItalyIRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro16132 Genova, ItalyDepartment of ExperimentalDiagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, ItalyCNR Institute of Organic Synthesis and Photoreactivity (ISOF)40129 Bologna, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM)16132 Genova, ItalyDepartment of Health Science (DISSAL)University of Genova, 16132 Genova, Italy davide.maggi@unige.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Maggi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin; D005947:Glucose
keywords: AMPK; Cancer; Glucose; Hexokinase; Metformin