Table 1.

Natural compounds regulating FoxOs.

Compounds	Sources	Efficacy	Molecular Mechanism	IC50(μM)	Cell line	References
Curcumin	Curcumalonga	Anti-proliferation	FOXO1, p-ERK1/2, p27, p21↑ Cyclin D1↓	10	A549 H460	[147]
Resveratrol	Phytopolyphenol	Cell growth arrest, Apoptosis	p-FOXO1, p-FOXO3a, p-FOXO4, p-PI3 K, p-AKT, p-Mtor, Cyclin D1↓ BimEL, BimL, BimS, p27, TRAIL, DR4, DR5↑	20	LNCaP	[148]
Capsaicin	Chili peppers (Capsicum)	Apoptosis Cell growth inhibition	p-FOXO1, p-JNK↓ Bim↑	50–150	BxPC-3, AsPC-1, Panc-1	[149]
Phorbol 12-myristate	Croton tiglium Linne	Anti-proliferation	p-FOXO1, Cyclin D3, CDK2, CDK4, CDK6, pRb, PKCζ, p-MAPK, pAKT↓	100	FRO	[150]
13-acetate		Cell cycle arrest	p21, p27, PKCα, PKCβ, PKCδ↑		ARO thyroid cancer
Apigenin	Ginkgo biloba L	Anti-proliferation Apoptosis	p-FOXO3a, p-AKT, Ki67, Cyclin D1↓, Bim↑	50	LNCaP, PC-3	[151]
Benzyl Isothiocyanate	Cruciferous vegetables	Apoptosis Cell growth suppression	p-PI3-K, p-AKT, p-FOXO1, p-FOXO3a↓, p27↑, p21↑, Bim↑	10	Capan-2, BxPC-3, AsPC-1	[152]
Aqueous Extract	Fagonia cretica	Cell Cycle Arrest Apoptosis	FOXO3a, γ-H2AX, Bax, p53, p21↑	2 μg/ml	MCF-7, MDA-MB-231	[153]
Epigallocatechin-3-Gallate	Grean tea	Anti-invasion	FOXO3a, E-Cadherin, γ-catenin, MTA3, Erα↑ Snail↓	20 μg	NF639, rel-3875, rel/CK2-5839	[154]
Isoflavone	Isoflavone mixture	Cell growth inhibition Apoptosis	p-FOXO3a, p-AKT, AR(androgen receptor) Karyopherin-α,Procaspase3↓ GSK-3β, p27, Activated caspase3↑	25 ∼ 50	Pca, LNCaP, C4-2B	[155]
18β-g glycyrrhetinic acid	Glycyrrhiza glaba L	Apoptosis Anti-proliferation	p-FOXO3a, Active caspase 9, Bim, Bax, Bak, Bad↑ caspase 9, Bcl-2, Bcl-xl, p-AKT, p-GSK-3β, c-Myc↓	100	MCF-7 MCF-10A	[156]
Casticin	Vitex rotundifolia L	Cell cycle arrest	p-FOXO3a, CDK1, CDC25B↓ p27↑	2 ∼ 10	Hep G2 PLC/PRF/5	[157]
Genistein	Iso flavonoid	Cell growth inhibition Apoptosis	FOXO3a, p-27, PTEN, p53, p65, p50↑ p-PDK1, p-AKT, p-GSK3β, P-IKBα, SIRT1↓	50	LNCaP PC-3	[158]
Baicalein	Flavonoid	Cell growth inhibition Apoptosis Ani-proliferation	FOXO3a, p-AMPKα, RUNX3, p-ERK1/2↑	75	PC9, H1299, H1650, A549, H358 H1975	[159]
Platycodin D	Platycodon grandiflorum	Cell Cycle Arrest Apoptosis Anti-proliferation	FOXO3a, p53, p21, p27, Bax, Cleaved caspase3, 8, 9↑ MDM2, Bcl-2, CDK1, CDK2, CDK4, CDK6. Cyclin D1, E2F1↓	5	PC3, LNCaP DU145 RWPE-1	[160]
Rhein	Rheum palmatum L	Apoptosis	p-FOXO3a, p-AKT↓ Cleaved caspase3, 7, Bim, p-elF2α, CHOP, Bid↑	75	MCF-10A MCF-7 HepG2	[161]
Vernodalin	Centratherum anthelminticum seeds	Cell ctycle arrest Apoptosis Tumor suppressor	FOXO3a, Bim, p21cip1/waf1, p21kip1↑ p-FOXO3a, Cyclin D1, Cyclin E, p-PI3 K, p-AKT↓	9.5	MCF-7 MDA-MB-231 LA7	[162]
Ergosterol	Amauroderma rude	Apoptosis Anti-invasion	FOXO3a, BimL, BimS, FasL↑	75	B16 MDA-MB-231 MDA-MB-468 MCF-7 SK-BR-3 4T1 NIH 3T3	[163]
Butein	polyphenol	Tumor suppressor	FOXO3a, Cyclin D1, p27, Bax↑ p-ERK1/2, p-AKT, Bcl-2↓	20	HeLa	[164]
Ardisianone	Croton tiglium Linne	Apoptosis Anti-proliferation Cell cycle arrest	p-FOXO3a, p-FOXO4, Pro-caspase 9, 8, 3, 7, Bcl-2, Bcl-XL, Mcl-1, Suvivin, p-AKT, p-mTOR, p-p70A6K↓ clAP1, clAP2,AIF, GRP78, Bak, Bid↑	6.3	PC-3 DU-145	[165]
Diterpenoid	Salvia miltiorrhiza	Apoptosis Tumor suppressor	p-FOXO3a↓ TrxR1, BimEL, BimL, BimS↑	10	HCT116 MEF	[166]
Isoorientin	Linum usitatissimum L	Apoptosis	FOXO4, Cleaved caspase 3, Cleaved PARP, Bax, Cyt C↑ p-AKT, HO-1↓	40	HepG2	[167]