Exploiting Methionine Addiction as a Potential Treatment Strategy for Cancer

Abstract

Cells require methionine not only for protein synthesis but also for nucleotide synthesis, methylation, and reductive metabolism, and indeed, these pathways support the high proliferative rate of cancer cells. Although different drugs (for example, methotrexate) that disrupt the methionine cycle have long been used for cancer treatment, they showed substantial side effects. Therefore, developing a newer generation of drugs with minimal side effects is necessary to treat cancer. Methionine is an essential amino acid processed through the methionine and folate cycle, and these pathways also give rise to two essential cellular antioxidants: hydrogen sulfide (H₂S) and glutathione (GSH). Due to the high proliferative rate, cancer cells depend on these pathways for methylation and the production of H₂S and GSH to maintain cellular homeostasis. On the other hand, due to the overuse of methionine, cancer cells also generate oxidative stress via the excessive production of homocysteine (Hcy). However, cancer cells handle this oxidative stress via the overproduction of H₂S and GSH. This article extensively discussed the methionine addition in cancer cells and how we can exploit this dependency on methionine to make a newer generation of drugs with minimal side effects.