Table 2.

Targets and cellular mechanism of flavonoids in prostate cancer (PCa). Flavonoids that exert anti-tumoral effect in PCa through epigenetic mechanisms are reported in the table. See text for details.

		Cell Lines/Animal Models/Clinical Trials	Molecular Target	Cellular Mechanism	Ref
Flavones	Apigenin	PC3-22Rv1 cells	↓ HDAC1, HDAC3 ↑ acetylation H3-H4	Cell cycle arrest apoptosis	[50]
		PC3 xenograft mice	↓ HDAC1, HDAC3	Tumor growth reduction	[50]
	Luteolin	PC3-LNCaP cells	↓ miR-301	Inhibition proliferation apoptosis	[121]
	+/- gefitinib	PC3 cells	↑ miR-603	Growth arrest Apoptosis	[124]
		PC3 cells	Binding to H4	Cell cycle arrest	[125]
	Morin + paclitaxel	DU145, PC3 cells DU145 xenograft mice	↓ miR-155 ↓ miR-155	Apoptosis Suppression of PCa progression	[131]
	Tricin + docetaxel	PC3 cells	↓ miR-21	Inhibition proliferation	[133]
Flavonols	Quercetin + hyperoside	PC3 cells	↓ miR-21	Apoptosis, cell cycle arrest and reduced invasive capacity	[139]
Flavanones	Silibinin	DU145, PC3 cells	↓ EZH2, ↑ DNMT ↓ HDAC1, HDAC2	Cell cycle arrest Apoptosis	[144]
Isoflavonoids	Genistein	LNCaP, LAPC-4 cells	↓ DNMT1, DNMT3b	Inhibition proliferation	[152]
		PC3, DU145 cells	↑ miR-34a, ↓ HOTAIR	Cell cycle arrest Apoptosis Inibition proliferation	[153]
Catechins	EGCG	PC3 cells	↓ DNMT	Cell growth inhibition	[165]
	EGCG	LNCaP cells	↓ HAT	Cell growth inhibition	[171]
	EGCG	LNCaP 22Rv1 cells 22Rv1 xenograft mice	↓ AR ↓ AR, miR-21, ↑ miR-330	Cell growth inhibition Suppression of PCa progression	[172]
	Polyphenon E	LNCaP, PC3 cells	↓ HDAC1, HDAC2, HDAC3, HDAC8 ↑ acetylation H3	Cell cycle arrest Apoptosis	[173]
	Polyphenon E	LNCaP cells	↓ DNMT1	Growth arrest	[174]
	Polyphenon E/EGCG	DUPRO, LNCaP cells Patients undergoing prostatectomy	↓ HDAC1, EZH2 ↓ HDAC1	Migration, invasion abrogation Suppression of PCa progression	[178]
Anthocyanidins	Delphinidin	LNCaP cell lines	↓ HDAC3	apoptosis	[181]

Histone deacetylase (HDAC), Enhancer of zeste homolog 2 (EZH2), histone acetyl transferase (HAT), DNA methyltransferase (DNMT), androgen receptor (AR), histone 3, 4 (H3, H4), HOX Transcript Antisense RNA (HOTAIR).