title: Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.
abstract: Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer.
authors.affiliation: Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.
authors.forename: Nagireddy
authors.initials: N
authors.lastname: Putluri
authors.forename: Ali
authors.initials: A
authors.lastname: Shojaie
authors.forename: Vihas T
authors.initials: VT
authors.lastname: Vasu
authors.forename: Srilatha
authors.initials: S
authors.lastname: Nalluri
authors.forename: Shaiju K
authors.initials: SK
authors.lastname: Vareed
authors.forename: Vasanta
authors.initials: V
authors.lastname: Putluri
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vivekanandan-Giri
authors.forename: Jeman
authors.initials: J
authors.lastname: Byun
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Sana
authors.forename: Steven M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: George
authors.initials: G
authors.lastname: Michailidis
authors.forename: Arun
authors.initials: A
authors.lastname: Sreekumar
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D008745:Methylation / Q000187:drug effects; D008954:Models, Biological; D009928:Organ Specificity / Q000187:drug effects; D010641:Phenotype; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000596:Amino Acids; D000728:Androgens