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Methionine Deprivation Induced Effects on the Growth of PC3 prostate cancer cells
Author(s) -
Diaz Eduardo,
Nosal Rebecca,
Venkatachalam KV
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.652.5
Subject(s) - methionine , cytosol , cysteine , cancer cell , cell growth , biochemistry , transfection , cell culture , biology , cytoplasm , glutathione , methylation , microbiology and biotechnology , chemistry , enzyme , cancer , gene , amino acid , genetics
Methionine is a key nutrient required for the synthesis of S‐adenosylmethionine (SAM). SAM is the universal methyl group donor. Methionine gamma lyase deaminase (Mgld) is an enzyme that degrades methionine into alpha‐ketobutyrate and methylthiol. In this study, the Mgld gene was cloned into vectors that expressed Mgld, either in the cytosol or in the nucleus. The prostate cancer cell line, PC3 (ATCC‐CRL1435) was transfected with vectors containing Mgld. The PC3 cells experience cell death when Mgld is expressed in the cytosol or nucleus. In the presence of Proparglycine (PGLY), a Mgld inhibitor, the cells proliferate to a moderate degree. Co‐treatment of the PGLY with the nuclear Mgld caused a slight decrease of cells whereas with cytoplasmic Mgld caused a slight increase. In the cytoplasm, methionine is required for forming cysteine; cysteine in turn is required for glutathione (cells redox agent). Both cysteine and methionine are required for protein synthesis. Therefore, cytosolic dwindling of methionine will hamper protein synthesis and it should, in general, affect the growth of Mgld treated cells when compared to controlled cells. The addition of PGLY alone or in combination with the cytosolic vector increased proliferation, while the addition of PGLY to the nuclear vector caused modest cell death. We conclude that the methylation status of PC3 might be different and it affects the growth in varying degrees depending on the location of the Mgld expression. We speculate that PGLY might affect expressed Mgld and endogenous cytosolic cystathione beta‐synthase activity, resulting in complex cell fate, a hypothesis that needs to be tested further. Support or Funding Information NSU Internal grant This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .