Dwindling Effects of Cytosolic and Nuclear Methionine Pools on Prostate, Ovarian and Pancreatic Cancer Cell Metabolism

Nova Southeastern University, Davie, Florida, USA

Objective. The effects of methionine gamma lyase-deaminase (Mgld) on cancer cells. Background. Methionine is a key nutrient required for various metabolic processes. In cytoplasm, methionine is often the first residue that is incorporated into proteins during synthesis. In cytosol, methionine is also activated into S-adenosylmethionine (SAM). SAM is the universal methyl group donor. There are many compounds that are either N or O methylated. Thus, altering the cytosolic methionine pool would result in various consequences that is expected to alter the cancer cells. In the nucleus, methylation of DNA promoter CpG islands suppresses the gene expression. Likewise, histone protein methylation results in heterochromatin formation causing gene suppression. Poor hnRNA-5’G-cap methylation results in destabilized RNA that are prone to degradation. In bacteria, free methionine is degraded by Mgld into methylthiol and the deaminated product a-ketobutyrate (a-KB). a-KB is a key nutrient that is metabolized by bacteria for energy purposes. Mgld is absent in humans. Therefore, methionine cannot be used for energy purposes in humans. Methods. In our lab, methionine levels are made lower in cells by transfecting plasmid vector that expresses the bacterial Mgld gene either in the cytosol or nucleus. The effects of cytosolic Mgld and nuclear Mgld were assessed and compared with the control non-transfected cell. Result. Our results show that there are differences in cancer cell metabolism due to either cytosolic or nuclear methionine deprivation. Conclusion. Methionine deprivation induced cytosolic and nuclear metabolism of prostate, ovarian and pancreatic cancer cells are different and the comparative analysis will be discussed. Grants. Supported by NSU HPD.