L-methionase: a therapeutic enzyme to treat malignancies.

Abstract

Cancer is an increasing cause of mortality and morbidity throughout the world. L-methionase has potential application against many types of cancers. L-Methionase is an intracellular enzyme in bacterial species, an extracellular enzyme in fungi, and absent in mammals. L-Methionase producing bacterial strain(s) can be isolated by 5,5'-dithio-bis-(2-nitrobenzoic acid) as a screening dye. L-Methionine plays an important role in tumour cells. These cells become methionine dependent and eventually follow apoptosis due to methionine limitation in cancer cells. L-Methionine also plays an indispensable role in gene activation and inactivation due to hypermethylation and/or hypomethylation. Membrane transporters such as GLUT1 and ion channels like Na(2+), Ca(2+), K(+), and Cl(-) become overexpressed. Further, the α-subunit of ATP synthase plays a role in cancer cells growth and development by providing them enhanced nutritional requirements. Currently, selenomethionine is also used as a prodrug in cancer therapy along with enzyme methionase that converts prodrug into active toxic chemical(s) that causes death of cancerous cells/tissue. More recently, fusion protein (FP) consisting of L-methionase linked to annexin-V has been used in cancer therapy. The fusion proteins have advantage that they have specificity only for cancer cells and do not harm the normal cells.

• Authors: Bhupender Sharma, Sukhdev Singh, Shamsher S Kanwar
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 506287 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25250324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Neoplasm Proteins
• Methionine
• Carbon-Sulfur Lyases
• L-methionine gamma-lyase

Topics

• Animals
• Carbon-Sulfur Lyases (therapeutic use)
• Humans
• Methionine (metabolism)
• Models, Biological
• Molecular Targeted Therapy (methods)
• Neoplasm Proteins (metabolism)
• Neoplasms (drug therapy, metabolism)