Table 4.

Natural products inhibiting metastasis.

Classification	Compound/Extract	Source	Cell Line/Animal Model	Dose; Duration	Efficacy	Mechanism	Ref.
Single compound	Flaccidoxide-13-acetate	Cladiella kashmani	RT4, T24	2.5, 5, 10 μM; 24 h	Inhibition of cell migration and invasion	↑TIMP-1, TIMP-2 ↓MMP-2, MMP-9, uPAR, FAK, PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR, Rho A, Ras, MKK7, MEKK3	[75]
Single compound	N-butylidenephthalide	Radix Angelica sinensis	5637, BFTC, T24, TCCSUP	60 μg/mL; 24 h	Inhibition of metastasis	↑E-cadherin ↓N-cadherin	[33]
Single extract	Extra virgin olive oil extract (EVOO-E)	Olea europaea L. var. Itrana	T24	2.5, 10 μg/mL; 24 h	Inhibition of cell migration and invasion	↑TIMP-1, TIMP-2 ↓MMP-2	[72]
Single extract	Garlic extract (GE)	Allium satibum L.	EJ	400, 600, 800 μg/mL; 24 h	Inhibition of cell migration and invasion	↓MMP-9, AP-1, Sp-1, NF-κB	[73]
Single extract	Sinulariolide	Sinularia flexibilis	TSGH-8301	800 μg/mL; 12, 24 h	Inhibition of cell migration and invasion	↑HSPA6	[74]

Footer: ↑, up-regulation; TIMP, metalloproteinase; ↓, down-regulation; MMP, matrix metalloproteinase; uPAR, urokinase-type plasminogen activator receptor; FAK, focal adhesion kinase; PI3K, phosphatidylinositide-3 kinases; AKT (PKB), protein kinase B; mTOR, mammalian target of rapamycin; Rho A, Ras homolog gene family, member A; Ras, regulators of signal transduction; MKK, mitogen-activated protein kinase kinase; MEKK (MAPKKK or MAP3K), Mitogen-Activated Protein Kinase Kinase Kinase; BFTC, Black Foot disease Transitional Carcinoma; TCCSUP, isolated from an anaplastic transitional cell carcinoma (TCC) in the neck of the urinary bladder; AP, activator protein; Sp, specificity protein; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TSGH, human gastric carcinoma cell line; HSPA6, Heat shock protein A6.