Prospective Epigenetic Actions of Organo-Sulfur Compounds against Cancer: Perspectives and Molecular Mechanisms

SIMPLE SUMMARY: Epigenetics has provided a new dimension to our understanding of cancer initiation and progression. Unlike the genetic changes in DNA sequence, abnormal epigenetic alterations may also lead to cancer development. Aberrant modulations in the functions of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are the fundamental events of the epigenome and contribute significantly to the pathogenesis of cancer. Interestingly, antioxidant, anti-proliferative, anti-inflammatory, anti-metastasis, anti-malarial, antiviral, antibacterial, and antifungal properties of plant-derived bioactive compounds have been extensively researched in recent decades. According to the American Cancer Society, there will be a 23.6 million increase in new cancer cases by 2030. Due to the severity of the increased risk, it becomes very important to develop novel drug candidates from natural sources and evaluate various preventive measures against cancer. Numerous studies have indicated that OSCs can target epigenetic mechanisms, representing an enticing strategy for therapeutic intervention. These OSCs, when administered in a dose-dependent and combinatorial-based manner, can have an enhanced impact on epigenetic alterations, which may lead to the cancer prevention and therapy. ABSTRACT: Major epigenetic alterations, such as chromatin modifications, DNA methylation, and miRNA regulation, have gained greater attention and play significant roles in oncogenesis, representing a new paradigm in our understanding of cancer susceptibility. These epigenetic changes, particularly aberrant promoter hypermethylation, abnormal histone acetylation, and miRNA dysregulation, represent a set of epigenetic patterns that contribute to inappropriate gene silencing at every stage of cancer progression. Notably, the cancer epigenome possesses various HDACs and DNMTs, which participate in the histone modifications and DNA methylation. As a result, there is an unmet need for developing the epigenetic inhibitors against HDACs and DNMTs for cancer therapy. To date, several epigenetically active synthetic inhibitors of DNA methyltransferases and histone deacetylases have been developed. However, a growing body of research reports that most of these synthetic inhibitors have significant side effects and a narrow window of specificity for cancer cells. Targeting tumor epigenetics with phytocompounds that have the capacity to modulate abnormal DNA methylation, histone acetylation, and miRNAs expression is one of the evolving strategies for cancer prevention. Encouragingly, there are many bioactive phytochemicals, including organo-sulfur compounds that have been shown to alter the expression of key tumor suppressor genes, oncogenes, and oncogenic miRNAs through modulation of DNA methylation and histones in cancer. In addition to vitamins and microelements, dietary phytochemicals such as sulforaphane, PEITC, BITC, DADS, and allicin are among a growing list of naturally occurring anticancer agents that have been studied as an alternative strategy for cancer treatment and prevention. Moreover, these bioactive organo-sulfur compounds, either alone or in combination with other standard cancer drugs or phytochemicals, showed promising results against many cancers. Here, we particularly summarize and focus on the impact of specific organo-sulfur compounds on DNA methylation and histone modifications through targeting the expression of different DNMTs and HDACs that are of particular interest in cancer therapy and prevention.