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

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.

Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers

“…Furthermore, SFN-mediated cytotoxic effects on HeLa, Cx, and CxWJ were seemingly envisaged to the modulation of cyclin B1 and GADD45β, thereby leading to G2/M cell cycle arrest [ 84 ]. SFN treatment also induced cell cycle arrest by epigenetic modulations of DNMT3b [ 85 ], as also highlighted in our recent review [ 69 ]. Furthermore, SFN treatment resulted in a significant decrease in the percentage of cells in the S and G2/M phases of the cell cycle, while there was a significant increment in the percentage of cells in the G1 phase, indicating SFN-induced G1 cell cycle arrest in SKOV-3 and OVCAR-3 cells [ 127 ].…”

“…Basically, for this review, we have followed the guidelines of the preferred reporting system for systematic reviews and meta-analysis (PRISMA). Different scientific databases including PubMed, Web of Science, Science Direct, Scopus, and Google Scholar were used to search the literature related to in vitro, in vivo, and human studies on anticancer potentials of respective ITCs [ 69 ]. Figure 1 highlights the molecular intricacies of the potential role of ITCs, whereas the studies highlighting the prospective role of ITCs against female-specific cancers have been collated in Table 2 .…”

Garlic‐derived compounds: Epigenetic modulators and their antitumor effects

“…DADS-treated cancer cells showed a decrease in cell proliferation and invasion by downregulating miR-222 and induced apoptosis by upregulating miR-34a (Shoaib et al, 2023).…”

“…For example, allicin increased the anti‐tumor effect of tamoxifen and reduced the liver damage caused by tamoxifen treatment (Shang et al, 2019). In addition, more and more recent studies focused on the epigenetic regulatory mechanism of garlic‐derived compounds, suggesting that they altered the expression of TSGs, oncogenes, and oncogenic miRNAs by regulating DNA methylation and histone modification in cancer (Shoaib et al, 2023). Although various studies have proposed many epigenetic mechanisms of anti‐tumor activity of garlic‐derived compounds, more researches are needed to further understand them.…”

“…The antitumor effect of DADS on breast cancer cells inhibited DNA synthesis and induced apoptosis. The apoptosis induced by DADS was due to the activation of Caspase‐3, downregulation of Bcl‐2 and Bcl‐xL, and increased expression of Bax, which may be a reaction to the inhibition and induction of HDACs, and the influence of DADS on the excessive acetylation of H4 (Shoaib et al, 2023). DADS‐induced transient histone hyperacetylation in various cancer cells (Druesne et al, 2004; Druesne‐Pecollo et al, 2008), DADS injection into rats has also been shown to increase histone acetylation (Druesne‐Pecollo et al, 2007).…”