Prostate cancer represents a major clinical public health challenge. Both epidemiological and clinical intervention studies support the protective role of
selenium against development of
prostate cancer. However, the mechanisms responsible for the inhibitory activity by this
micronutrient remain elusive. Furthermore, literature reports consistently have shown that the dose and form of
selenium are important factors in
cancer chemoprevention. Thus, in the present investigation using
androgen responsive (AR) lymph node
carcinoma of the prostate (LNCaP) and its
androgen-independent clone (AI) LNCaP C4-2 human
prostate cancer cells, we compared the effects of
selenomethionine (SM) and
1,4-phenylenebis(methylene)selenocyanate (p-XSC) on cell growth,
DNA synthesis, and on proteomic profiles. p-XSC (5-20 microM) significantly inhibited cell growth in both cell types in a dose-dependent manner; SM was also effective but at much higher doses (50-100 microM). We hypothesize that the inhibition of cell growth is due, in part, to
selenium interaction with redox-sensitive
proteins. Using 2D gel electrophoresis, both
organoselenium compounds altered the expression, to a varied extent, of several unrecognized
selenium-responsive
proteins. Employing matrix-assisted
laser-desorption ionization (MALDI) and time-of-flight (TOF; MALDI-TOF) followed by tandem mass spectrometric analysis, we identified the following
proteins:
cofilin-2,
heterogeneous nuclear ribonucleoprotein, single-stranded
mitochondrial DNA binding protein,
chaperonin 10,
nucleoside diphosphate kinase 6, and chain A Horf 6 human
peroxidase enzyme. This is the first report showing that SM and p-XSC are capable of altering these
proteins; their roles in
prostate cancer prevention warrant further investigations.