Differential effects of naturally occurring and synthetic organoselenium compounds on biomarkers in androgen responsive and androgen independent human prostate carcinoma cells

Epidemiological studies and clinical trials show that selenium supplementation results in reduction of prostate cancer incidence; however, the form of selenium and mechanisms underlying protection remain largely unknown. Toward this end, we compared the effects of naturally occurring selenomethionine (SM) and Se‐methylselenocysteine (MSC) and synthetic 1,4‐phenylenebis(methylene)selenocyanate (p‐XSC) and p‐xylylbis(methylselenide) p‐XMS) organoselenium compounds in androgen responsive (AR) LNCaP and its androgen independent clone (AI) LNCaP C4‐2 human prostate carcinoma cells on cell growth, secretion of prostate specific antigen (PSA), intracellular redox status and genomic profiles with emphasis on identifying redox sensitive genes. Both p‐XSC and p‐XMS reduced cell number and total protein concentration compared to control‐treated AR and AI cells, while SM and MSC exhibited no effect on growth of AR and AI cells. SM, p‐XSC and p‐XMS but not MSC inhibited levels of secreted PSA in AR cells. SM, MSC and p‐XMS increased glutathione (GSH) levels in AI LNCaP cells. By contrast, in both cell types, only p‐XSC significantly decreased GSH concentrations to