Because the
Selenium (Se) and
Vitamin E Cancer Prevention Trial (SELECT) failed to show the efficacy of
selenomethionine for
prostate cancer prevention, there is a critical need to identify safe and efficacious Se forms for future trials. We have recently shown significant preventive benefit of
methylseleninic acid (MSeA) and
Se-methylselenocysteine (MSeC) in the transgenic
adenocarcinoma mouse prostate (TRAMP) model by
oral administration. The present work applied iTRAQ proteomic approach to profile
protein changes of the TRAMP prostate and to characterize their modulation by MSeA and MSeC to identify their potential molecular targets. Dorsolateral prostates from wild-type mice at 18 weeks of age and TRAMP mice treated with water (control), MSeA, or MSeC (3 mg Se/kg) from 8 to 18 weeks of age were pooled (9-10 mice per group) and subjected to
protein extraction, followed by protein denaturation, reduction, and alkylation. After tryptic digestion, the
peptides were labeled with iTRAQ
reagents, mixed together, and analyzed by two-dimensional liquid chromatography/tandem mass spectrometry. Of 342
proteins identified with >95% confidence, the expression of 75
proteins was significantly different between TRAMP and wild-type mice. MSeA mainly affected
proteins related to prostate functional differentiation,
androgen receptor signaling,
protein (mis)folding, and endoplasmic reticulum-stress responses, whereas MSeC affected
proteins involved in phase II detoxification or cytoprotection, and in stromal cells. Although MSeA and MSeC are presumed precursors of
methylselenol and were equally effective against the TRAMP model, their distinct affected
protein profiles suggest
biological differences in their molecular targets outweigh similarities.