Epigenetics of Prostate Cancer and Novel Chemopreventive and Therapeutic Approaches

Prostate cancer is a commonly diagnosed cancer and a leading cause of male cancer-related mortality. Risk factors associated with prostate cancer include age, race, family history, and dietary factors. Although several etiological factors govern prostate cancer occurrence, epigenetic mechanisms are an important means of gene regulation in prostate cancer. In this chapter, we will briefly review the causal genomic factors involved in prostate tumorigenesis and will then elaborate on the roles of different epigenetic components, including DNA methylation, histone modifications, microRNAs, and their alterations in prostate tumor cell lines and in patient-derived tumors. Frequent epigenetic aberrations, such as DNA hypermethylation and hypomethylation as well as altered histone acetylation and methylation, have been observed in prostate cancer leading to tumorigenesis, tumor progression, and metastasis. In addition, small noncoding RNAs such as microRNAs are involved in regulating the prostate cancer epigenome. Recent studies have highlighted the important cross talk between microRNAs and cellular epigenetic mechanisms and will be discussed here. Further, dietary factors/nutraceuticals play an important role in regulation of the epigenome and the chemoprevention of prostate cancer. In this chapter, we examine the current literature regarding diet-mediated epigenetic alterations in prostate cancer with a particular focus on microRNAs. We will review how different dietary components regulate DNA methylation, histone modifications, and microRNA expression and can be utilized as chemopreventive agents in prostate cancer.