Potential Anticancer Properties and Mechanisms of Action of Formononetin

Table 2

Molecular targets of Formononetin in different types of cancer.

Cancer types	Cell lines	Treatment time	IC50	Molecular targets	Cell cycle arrest	References
Ovarian	ES2,OV90	48 h	40 μM	p38↑, ERK1/2↓, P90RSK↓, AKT↓, P70S6K↓, ROS↑	G0/G1	[10]
	SKOV3	24 h	283.5 μM	caspase3/9↑, Bax/Bcl2↑, MMP-2, MMP-9, p-ERK↓	- -	[34]
		48 h	209.3 μM
	A2780	24 h	310.0 μM
		48 h	186.1μM
Breast	MDA-MB-231, MCF-7,; SK-BR-3	24 h	50 μg/ml	p-GS3Kβ⊥, p-PI3K, p-mTOR↑, p-AKT	- -	[35]
	MCF-7 WS8	48 h	10 μg/ml	CYP1A1↓, P450 1A1↑	- -	[36]
	MCF-7	24, 48h	50 μM	ERα↑, miR-375↑, Bcl-2↓, p-AKT↑	- -	[37]
	4T1, MDA-MB-231	24 h	160 μM	TIMP-2↑, TIMP-1↑, MMP-9↓, MMP-2↓	- -	[38]
	MDA-231, MDA-435	24, 48, 72 h	100 μM	ERβ↑, IGF-1R↓, PARP-, miR-375↓	- -	[39]
	MCF-7	24, 48, 72 h	100 μM	GF1/IGF1R-PI3K/ , cyclin D1↓, Bax/Bcl-2↑, Ras-p38MAP,	- -	[40]
Colon	SW1116,HCT116	24 h	200 μM	cyclin D1↓, (MMP)2, MMP9, (miR)149↑, EphB3↓, PI3K/AKT, STAT3	G0/G1	[41]
Hepatoma	HuH-7	24 h	20 μM	- -	- -	[18]
Cervical	HeLa, SiHa, CaSKi	24 h	25 Μm	ROS↓, JNK, caspase-, caspase-, Bax/Bcl2↑, PI3K/AKT	- -	[42]
Laryngeal	Hep-2	24, 48 h	50 and 75 μg/ml	ROS↓, CdCl2	G0/G1	[23]
Lung	A549	48 h	60 mg/ml	p-Smad 2/3↓, TGF-β1, EMT	- -	[43]
	A549, NCI-H23	24 h	100 μM	p53↑, p21↑, cyclin A↓, cyclin D1↓,	G1	[44]
Bladder	T24	24 h	200 μM	T24, PTEN↑, p- AKT ↓, miR-2	- -	[45]
Gastric	MGC-803	- -	- -	- -	- -	[46]
Esophagus	EC-109	- -	- -	- -	- -	[46]
Prostate	PC3	48 h	1.97 μM	p-ERK↓, p-JNK↓, c-Myc↓ p-p38↓, cyclin B1↓, cyclin A↓, cyclin D1↓, CDK4↓, Axin↑, β-catenin↓, TCF-4↓	G1	[46]
	DU145, PC3	48 h	200 μM	Bcl-2↓, RASD1↑, Bax↑, IGF-1 R↓	- -	[47]
	PC3	48 h	>12.5 μM			[48]
	PC-3, DU145	48 h	80μM	AKT /cyclin D1/CDK4↓	G0/G1	[49]
Nasopharyngeal	CNE2	24 h	1 μM	Bax↓, bcl-2↑, p-ERK1/2↑	- -	[50]
Adrenal medulla	PC12	24 h	20 μg/ml	ROS↑, MDA↓, GSH↓	- -	[51]
Multiple myeloma	U266, RPMI8226	48 h	100 μM	STAT3↓, STAT5↓, JAK1↓, JAK2↓, cSrc↓, ROS↑, caspase-, PAR	- -	[52]
Osteosarcoma	U2OS	48 h	80 μM	Bax↑, ↓, miR-375↓, caspase-3↑, ,	- -	[53, 54]
Glioma	U87MG, U251MG, T98G	24,48 h	100 μM	E-cadherin↓, HDAC5↑	- -	[54]

Downregulation↓, Upregulation ↑, Activation , Inhibition, Bax: Bcl-2 associated x protein, Bcl-2: B-cell lymphoma, JNK: c-Jun-N-terminal kinase, MAPK: mitogen activated protein kinase, mTOR: mammalian target of rapamycin, Cdks: cyclin dependent kinases, EKR: extracellular signal-regulated kinase.