Exploiting methionine restriction for cancer treatment

Biochem Pharmacol. 2018 Aug;154:170-173. doi: 10.1016/j.bcp.2018.05.003. Epub 2018 May 4.

Abstract

Normal cells can synthesize sufficient methionine for growth requirements from homocysteine and 5-methyltetrahydrofolate and vitamin B12. However, many cancer-cell types require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) deficiency is associated with methionine dependence in cancer cells, there are other causes for tumors to require exogenous methionine. In this review we describe studies that show restricting methionine to certain cancers by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics is a promising antitumor strategy. The basis for methionine dependence in tumor cells is also briefly reviewed.

Keywords: 5-Methyltetrahydrofolate; MTAP; Methioninase; Methionine; Methionine restriction; Vitamin B12.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic / methods
  • Humans
  • Methionine / metabolism*
  • Methionine / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Purine-Nucleoside Phosphorylase / metabolism
  • Tetrahydrofolates / metabolism
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Tetrahydrofolates
  • Methionine
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase
  • 5-methyltetrahydrofolate