Metformin, cancer and glucose metabolism

Barbara Salani, Alberto Del Rio, Cecilia Marini, Gianmario Sambuceti, Renzo Cordera, Davide Maggi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)R461-R471
JournalEndocrine-Related Cancer
Volume21
Issue number6
DOIs
Publication statusPublished - Dec 1 2014

    Fingerprint

Keywords

  • AMPK
  • Cancer
  • Glucose
  • Hexokinase
  • Metformin

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Salani, B., Del Rio, A., Marini, C., Sambuceti, G., Cordera, R., & Maggi, D. (2014). Metformin, cancer and glucose metabolism. Endocrine-Related Cancer, 21(6), R461-R471. https://doi.org/10.1530/ERC-14-0284