Arene-Ruthenium(II)/Osmium(II) Complexes Potentiate the Anticancer Efficacy of Metformin via Glucose Metabolism Reprogramming

Angew Chem Int Ed Engl. 2022 Sep 19;61(38):e202208570. doi: 10.1002/anie.202208570. Epub 2022 Aug 11.

Abstract

Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1-6 with oxoglaucine derivatives as ligands were synthesized and their anti-tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.

Keywords: Cancer; Glucose Metabolism; Intermittent Fasting; Metformin; Oxoaporphine Arene-Ruthenium(II)/Osmium(II).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes* / pharmacology
  • Glucose
  • Humans
  • Hypoglycemia*
  • Metformin* / pharmacology
  • Organometallic Compounds*
  • Osmium
  • Ruthenium* / pharmacology

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Organometallic Compounds
  • Osmium
  • Ruthenium
  • Metformin
  • Glucose