School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai, United Arab Emirates.
Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia.
Semin Cancer Biol. 2022 Aug;83:353-376. doi: 10.1016/j.semcancer.2020.12.021. Epub 2021 Jan 9.
Cell cycle, growth, survival and metabolism are tightly regulated together and failure in cellular regulation leads to carcinogenesis. Several signaling pathways like the PI3K, WNT, MAPK and NFKb pathway exhibit aberrations in cancer and help achieve hallmark capabilities. Clinical research and in vitro studies have highlighted the role of epigenetic alterations in cancer onset and development. Altered gene expression patterns enabled by changes in DNA methylation, histone modifications and RNA processing have proven roles in cancer hallmark acquisition. The reversible nature of epigenetic processes offers robust therapeutic targets. Dietary bioactive compounds offer a vast compendium of effective therapeutic moieties. Isothiocyanates (ITCs) sourced from cruciferous vegetables demonstrate anti-proliferative, pro-apoptotic, anti-inflammatory, anti-migratory and anti-angiogenic effect against several cancers. ITCs also modulate the redox environment, modulate signaling pathways including PI3K, MAPK, WNT, and NFkB. They also modulate the epigenetic machinery by regulating the expression and activity of DNA methyltransferases, histone modifiers and miRNA. This further enhances their transcriptional modulation of key cellular regulators. In this review, we comprehensively assess the impact of ITCs such as sulforaphane, phenethyl isothiocyanate, benzyl isothiocyanate and allyl isothiocyanate on cancer and document their effect on various molecular targets. Overall, this will facilitate consolidation of the current understanding of the anti-cancer and epigenetic modulatory potential of these compounds and recognize the gaps in literature. Further, we discuss avenues of future research to develop these compounds as potential therapeutic entities.
细胞周期、生长、存活和代谢紧密调节在一起，细胞调节的失败导致致癌。几种信号通路，如 PI3K、WNT、MAPK 和 NFKb 通路，在癌症中表现出异常，有助于实现标志性特征。临床研究和体外研究强调了表观遗传改变在癌症发生和发展中的作用。DNA 甲基化、组蛋白修饰和 RNA 处理的改变导致的基因表达模式的改变，已被证明在获得癌症标志性特征中发挥作用。表观遗传过程的可逆性提供了强大的治疗靶点。膳食生物活性化合物提供了广泛的有效治疗药物。源自十字花科蔬菜的异硫氰酸盐（ITCs）对多种癌症具有抗增殖、促凋亡、抗炎、抗迁移和抗血管生成作用。ITCs 还可调节氧化还原环境，调节 PI3K、MAPK、WNT 和 NFkB 等信号通路。它们还通过调节 DNA 甲基转移酶、组蛋白修饰酶和 miRNA 的表达和活性来调节表观遗传机制。这进一步增强了它们对关键细胞调节剂的转录调节作用。在这篇综述中，我们全面评估了异硫氰酸酯（如萝卜硫素、苯乙基异硫氰酸酯、苄基异硫氰酸酯和烯丙基异硫氰酸酯）对癌症的影响，并记录了它们对各种分子靶点的作用。总的来说，这将有助于巩固人们对这些化合物的抗癌和表观遗传调节潜力的现有认识，并认识到文献中的空白。此外，我们讨论了未来研究的途径，以开发这些化合物作为潜在的治疗实体。
