Multidimensional protein identification technology analysis highlights mitoxantrone-induced expression modulations in...

Chemotherapeutic agents as they are used today have limited effectiveness against prostate cancer, but may potentially be used in new combinations with more efficacious results. Mitoxantrone, used for palliation of prostate cancer, has recently been found by our group to improve the susceptibility of primary prostate cancer cells to killing through the Fas-mediated death pathway. Here we used a shotgun proteomics approach to first profile the entire prostate cancer proteome and then identify specific factors involved in this mitoxantrone response. Peptides derived from primary prostate cancer cells treated with or without 100 nM mitoxantrone were analyzed by multidimensional protein identification technology (MudPIT). Strict limits and data filtering hierarchies were applied to identify proteins with high confidence. We identified 1498 proteins belonging to the prostate cancer proteome, 83 of which were significantly upregulated and 27 of which were markedly downregulated following mitoxantrone treatment. These proteins perform diverse functions, including ceramide production, tumour suppression, and oxidative reduction. Detailed proteomic analyses of prostate cancer cells and their response to mitoxantrone will further our understanding of its mechanisms of action. Identification of proteins influenced by treatment with mitoxantrone or other compounds may lead to the development of more effective drug combinations against prostate cancer.