Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway

Table 1

The epigenetic regulation of sulforaphane (SFN) in cancer.

Epigenetic mechanisms	Cancer types	Epigenetic functions	Target genes/proteins	Anticancer effects	References
Histone acetylation	Prostate cancer cells (LnCaP and PC-3) and PC-3 cell xenografts	Inhibition of class I and II HDACs	Reactivation of p21 and Bax	Cell cycle arrest and apoptosis↑	[42, 45, 49]
	Colon cancer cells (HCT116)	Inhibition of HDAC3	CtIP: a critical DNA repair protein	DNA damage and apoptosis↑	[43]
			Acetylation of CtIP and its degradation
	Lung cancer cells (A549 and H1299) and A549 cell xenografts	Inhibition of HDAC activity	Reactivation of p21 and Bax	Cell growth↓	[44]
				Apoptosis↑
Histone phosphorylation	Bladder cancer cells (RT4, J82, and UMUC3) and UMUC3 cell xenografts	Inhibition of histone H1 phosphorylation	Increased PP1β and PP2A phosphatase	Carcinogenesis and progression↓	[55]
DNA methylation	Prostate cancer cells (LNCap)	Decreased expression of DNMT1 and 3b	Restoration of cyclin D2	Cancer cell death↑	[59]
	Human breast cancer cells (MCF-7 and MDA-MB-231)	Inhibition of DNMT1 expression	Restoration of P21, PTEN, and RARbeta2	Cell growth arrest and apoptosis↑	[61]
	Human breast cancer cells (MCF-7 and MDA-MB-231)	Decrease in DNMT1 and 3a expression and activity	Downregulation of hTERT expression	Apoptosis↑	[58]
	Cervical cancer cells (HeLa)	Inhibition of DNMT3b activity	Upregulation of RARβ, CDH1, DAPK1 and Bax	Cell cycle arrest and apoptosis↑	[60]
Noncoding RNA regulation	Oral squamous carcinoma cells (SAS and GNM); cancer stem cell xenografts (SAS and GNM)	Induction of miR-200c	Suppression of Bmi1	Cell migration, invasiveness, and growth↓	[65]
	95D and H1299 cells and in vivo xenografts	Downregulation of miR-616-5p	Inactivation of the GSK3β/β-catenin pathway	EMT and metastasis↓	[6]
	Human glioma cell lines (H4, SNB19, LN229, and U251) and colorectal cancer cells	Downregulation of miR 21	Inhibition of the Wnt/β-catenin pathway	Apoptosis↑	[66, 67]
				Cell viability↓
	Prostate cancer cells (LNCaP and PC-3)	Decreased expression of the lncRNA LINC01116		Cell proliferation↓	[69]
CPG demethylation and histone acetylation at the Nrf2 promoter	Mouse skin epidermal JB6 (JB6 P+) cells and prostate cancer (TRAMP C1) cells	Inhibition of DNMT1, 3a, and 3b and HDAC1–5 and HDAC7	The reactivation of Nrf2	Cell transformation and development↓	[20, 21]