Table 1.

Effects and molecular targets of icariin and icariside II on different cancer cell lines.

Cancer Types	Components	Cell Lines	Concentrations		Effects and Molecular Targets	Reference
			Con. Range	IC50
Hepatocellular carcinoma	Icariin	HepG2	10 μM	NA	G0/G1↑, S↓, Bcl-2↓	[37]
		SMMC-7721	5–20 μM	around 10 μM	cleaved caspase-3/9↑, mitochondria cytochrome c↓, cytosol cytochrome c↑, cleaved PARP1↑, XIAP↓, MMP↓, Bcl-2↓, Bax↑, p-JNK↑, ROS↑	[38]
Prostate carcinoma	Icariin	PC-3	30 μM	NA	Cyclin D1↓, CDK4↓	[39]
	Icariside II	PC-3	0–40 μM	around 20 μM	MMP↓, cleaved caspase-3/8/9↑, cleaved PARP↑, COX-2↓, iNOS↓, VEGF↓, PGE2↓	[40]
Esophageal cancer	Icariin	EC109	20–80 μM	106.13 μM (12 h)	cleaved caspase-9↑, ROS↑, NADPH oxidase activity↑, GSH↓, GRP78↑, ATF4↑, CHOP↑, p-PERK↑, p-eIF2α↑, Bcl2↓, PUMA↑	[41]
				73.65 μM (24 h)
				38.59 μM (36 h)
		TE1	20–80 μM	115.29 μM (12 h)
				76.77 μM (24 h)
				42.21 μM (36 h)
Ovarian cancer	Icariin	A2780	13–50 μM	NA	caspase-3 activity↑, miR-21↓ PTEN↑ RECK↑ Bcl-2↓	[42]
Lung cancer	Icariin	A549	25–100 μM	118.25 μM (12 h)	ROS↑, caspase 3 activity↑, GSH↓, ERS-related molecules↑(p-PERK, ATF6, GRP78, p-eIF2a, and CHOP), Bcl-2↓, PUMA↑	[43]
				86.21 μM (24 h)
				56.8 μM (36 h)
	Icariside II	A549	0–20 µM	NA	vimentin↓, N-cadherin↓, NF-κB↓, p-IκBα↓, p65/IκB↑, p-Akt↓ p-GSK-3β↓	[44]
		H1299	0–20 µM	NA
Melanoma	Icariin	B16	20–200 μg/mL	84.3μg/mL (72 h)	procaspase-9↓ cleaved caspase-9↑	[45]
	Icariside II	A375	0–100 μM	10.6 μM	G0/G1 phase↑, S↓, G2/M arrest↑, cyclin E↓, CDK2↓, cyclin B1↓, P‑CDK1↓, ROS↑, p-p38↑, p-p53↑, p21↑, cleaved caspase-3↑, survivin↓, p-STAT3↓, p-ERK↓, cleaved PARP↑	[46,47,48]
		SK-MEL-5	0–100 μM	11.1 μM
Leydig cell tumor	Icariin	MLTC-1	12.5–100 μg/mL	50 μg/mL (48 h)	S↓, Bcl-2↓, Bax↑, cytochrome c↑, cleaved caspase-3/9↑, piwil4↓	[49]
Gastric adenocarcinoma	Icariin	BGC-823	20–200 μg/mL	128 μg/mL	Rac1↓, VASP↓	[50]
Medulloblastoma	Icariin	Daoy	NA	NA	Cyclin A↓, CDK2↓, Cyclin B1↓, cleaved caspase-3↑, cleaved caspase-9↑, PARP↑, Bcl-2↓	[51]
		D341	NA	NA
Sarcoma	Icariside II	U2OS	0–30 µM	NA	4E-BP1↑, mTORC1↓, p-S6K(Thr389)↓, p-S6(Ser235/236)↓, p-4E-BP1 (Ser65)↓	[52]
		SW1353	0–20 µM	NA
		S180	0–20 µM	NA
Hepatoblastoma	Icariside II	HepG2	0–30 μM	NA	△ψm↓, ROS↑, Bax/Bcl-2↑, cleaved-Bid↑, LAMP1↑, LMP↑, cleaved caspase-8/9/7/3/PARP↑, LC3B-II↑, SQSTM1↑	[53]
Osteosarcoma	Icariside II	MG-63	10–35 μM	NA	p-EGFR↓, p-PI3K↓, p-Akt↓, p-PDK1↓, p-Raf↓, p-mTOR↓, p-PDK1↓, p-PRAS40↓, p-GSK3β↓, p-ERK↓	[54]
		Saos-2	10–35 μM	NA
		HOS	0–10 μM	NA	HIF-1α↓, VEGF↓, uPAR↓, ADM↓, MMP2↓, Glut4↓, MCT4↓, aldolase A↓, enolase 1↓	[55]
Epidermoid carcinoma	Icariside II	A431 cell line	0–100 μM	NA	cleaved caspase 9↑, cleaved PARP↑, caspase 9↓, PARP↓, p-STAT3↓, p-ERK↓, p-AKT↑, p-EGFR↑↓	[56]
Acute myeloid leukemia	Icariside II	U937	0–50 μM	NA	cleaved PARP↑, procaspase 3↓, Bcl-2↓, Bcl-XL↓, survivin↓, COX-2↓, p-STAT3↓, p-JAK2↓, p-Src↓	[57]
Breast cancer	Icariside II	MCF-7	0–100 μM	72.73 μM (24 h)	MMP↓, cleaved caspase-3/7/8/9↑, cleaved PARP↑, △ψm↓, cytosol cyto c↑, cytosol AIF↑, mitochondrial cyto c↓, mitochondrial AIF↓, Fas↑, FADD↑, Bcl-xL↑, Bax↑, BimL↑	[58]
				57.98 μM (48 h)
				50.95 μM (72 h)
				37.75 μM (96 h)
		MDA-MB-231	0–100 μM	97.14 μM (24 h)
				62.75 μM (48 h)
				42.40 μM (72 h)
				38.65 μM (96 h)
Multiple myeloma	Icariside II	U266	0-100 μM	NA	p-STAT3↓, p-JAK2↓, p-c-Src↓, SHP-1↑, PTEN↑, cyclin D1↓, Bcl-2↓, Bcl-xL↓, survivin↓ VEGF↓, COX-2↓, cleaved caspase-3↑, p-PARP↑	[59]

NA, not applicable; ↑, up-regulation; ↓, down-regulation.