Abnormal epigenetic alterations are one of the keystones of cancer development. Epigenetic targeting drugs have become a promising and effective cancer therapy strategy. However, due to the high toxicity and unclear mechanisms of action of these drugs, natural compounds that cause epigenetic modulation have also been studied. Sulforaphane (SFN) is a promising bioactive compound for epigenetic targeting therapy. In this study, we investigate the effects of SFN on gene expression and DNA methylation in human hepatocellular carcinoma cells (HepG2). Using high throughput technologies in combination with cell-based assays, we find SFN is a potent anticancer agent, as it induces DNA damage, mitotic spindle abnormalities followed by apoptosis and proliferation inhibition in HepG2 cells. Our results show the upregulation of DNA damage response and cell cycle checkpoint genes. Also, we find the downregulation of cellular pathways frequently overexpressed in human cancer. As expected, SFN exerts epigenetic modulation effects by inhibiting histone deacetylases (HDACs). SFN might affect the activity of oncogenic transcription factors through methylation of its binding sites motifs. Our findings offer insights into SFN chemopreventive molecular effects in HepG2 cells and highlight SFN as a valuable natural approach to cancer therapy for future investigation.

中文翻译：

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萝卜硫烷调节的转录组和DNA甲基化变化诱导人肝癌细胞的细胞周期停滞，凋亡，DNA损伤和增殖抑制。

异常的表观遗传学改变是癌症发展的基石之一。表观遗传靶向药物已成为一种有前途和有效的癌症治疗策略。然而，由于这些药物的高毒性和不清楚的作用机理，还研究了引起表观遗传调控的天然化合物。萝卜硫烷（SFN）是用于表观遗传靶向治疗的有前途的生物活性化合物。在这项研究中，我们调查了SFN对人肝癌细胞（HepG2）基因表达和DNA甲基化的影响。通过将高通量技术与基于细胞的测定相结合，我们发现SFN是有效的抗癌剂，因为它会诱导DNA损伤，有丝分裂纺锤体异常，然后诱导HepG2细胞凋亡和增殖抑制。我们的结果显示了DNA损伤反应和细胞周期检查点基因的上调。此外，我们发现在人类癌症中经常过度表达的细胞通路的下调。如预期的那样，SFN通过抑制组蛋白脱乙酰基酶（HDAC）发挥表观遗传调控作用。SFN可能通过其结合位点基序的甲基化影响致癌转录因子的活性。我们的发现提供了关于HepG2细胞中SFN化学预防分子作用的见解，并强调了SFN是一种有价值的天然癌症治疗方法，可用于未来的研究。SFN可能通过其结合位点基序的甲基化影响致癌转录因子的活性。我们的发现提供了关于HepG2细胞中SFN化学预防分子作用的见解，并强调了SFN是一种有价值的天然癌症治疗方法，可用于未来的研究。SFN可能通过其结合位点基序的甲基化影响致癌转录因子的活性。我们的发现提供了关于HepG2细胞中SFN化学预防分子作用的见解，并强调了SFN是一种有价值的天然癌症治疗方法，可用于未来的研究。