Monitoring In Vitro Response of Selenium-Treated Human Prostate Cells by 1H NMR Spectroscopy
Keywords:NMR spectroscopy, metabolomics, selenomethionine, Se-methylselenocysteine, prostate cancer, apoptosis
NMR metabolomics provides a potent method for monitoring alterations in the metabolic signature within tissues and biofluids. In this study, NMR analysis was utilized to determine variation in metabolite levels of human DU145 prostate cancer and non-tumorigenic PNT1A prostate epithelial cells after treatment with selenomethionine (SeM) and Se-methylselenocysteine (SeMSC). Currently, these are the first 1H NMR spectroscopic data on selenium-treated prostate cell lines. Fluorescence microscopy of SeMincubated PNT1A cells revealed morphological features characteristic of apoptosis. SeMSC-treated PNT1A and DU145 prostate cells indicated greater changes in cellular morphology and in metabolite levels than SeMtreated cells. NMR of prostate cells treated with selenium showed a decreasing trend in metabolite levels with the largest change exhibited by creatine. This is mainly due to disrupted energy metabolism, and probably due to loss of structural integrity combined with dissipation of metabolites. Lactate, choline-containing compounds, and glycine levels increased depending on the type of selenium and cell line used. No clear pattern of variation in metabolite concentration levels from 1H NMR spectroscopy to distinguish apoptotic versus non-apoptotic pathway was observed. Factor analysis (FA) indicated the change in the concentration levels of twelve metabolites was able to distinguish DU145 cells from PNT1A cells when treated using SeM. This study indicated that NMR of intact cells treated with selenium can provide information on the biochemical processes of tissues; thus metabolic fingerprints for compromised cells can be acquired.