Table 2.

Phytochemicals with anti-EMT properties

Phytochemicals	Effects	In vitro studies	In vivo studies	References
Fisetin	↓ Nuclear localization of β-catenin	MEL-928, WM-35		[140]
	↓ pMEK1/2, pERK1/2, nuclear localization of NFκB	A375, RPMI-7951		[141]
	↓ pAKT, p70SK6, pmTOR	A375, 451Lu	A375, 451Lu melanoma xenografts	[142]
	↓ Invasion, metastasis ↓ N-cadherin, vimentin, fibronectin, MMPs ↑ E-cadherin, desmoglein ↓ Snail1, Zeb1, Twist1, Slug	A375, SK-MEL-28	A375, SK-MEL-28 subcutaneously injected in athymic nude mice	[121]
	↓ Radial to vertical transition	A375		[142]
Epigallocatechin gallate (EGCG)	↓ Migration, ↑ E-cadherin	A375		[146]
	↓ Migration	B16		[147]
	↓ Invasion	B16F10		[148]
	↓ Adhesion, α2β1 integrin	A2508		[149]
	↓ Adhesion	B16		[150]
	↓ Vimentin, fibronectin, N-cadherin ↑ E-cadherin, desmoglein, cytokeratin	A375, Hs294t		[145]
	↓ MMP-2, pERK1/2	M17		[151]
	↓ pFAK, MMP-9	B16		[152]
	↓ Metastasis		C57BL/6 mice subcutaneously injected with B16F10	[148]
	↓ Lung metastasis		B16F10 and B16- F3m cells intraperitonally inoculated in Balb/c mice	[152]
Proanthocyandins	↓ Migration, COX-2, PGE2 ↑ E-cadherin ↓ N-cadherin, vimentin, fibronectin, Slug ↓ ERK1/2, NFκB	A375, Hs294t		[156]
	↓ β-catenin expression, MMPs, MITF, ↓ PI3K/AKT signaling ↓ Migration	A375, Hs294t, MEL-1241		[157]
	↓ β-catenin expression, PGE2, MMPs		Athymic nude mice intravenously injected with A375 cells	[157]
Apigenin	↓ Motility, migration ↓ STAT-3 nuclear localization ↓ N-cadherin, fibronectin, MMPs, Twist1 ↑ Keratin-8, E-cadherin	A375, G361		[159]
	↓ Integrins, pFAK, pERK1/2	A2058, A375		[160]
	↑ Cadherin-catenin complexing	518A2		[161]
	↓ Lung metastasis, VCAM1		B16-BL6 melanoma cells injected in lateral tail vein of C57BL/6N mice	[162,163]
Quercetin	↓ Invasion	B16-BL6		[162]
	↓ Migration, Invasion ↓ pSTAT-3, Src, JAK2 ↑ pAKT, pERK	A375, A2058		[164]
	↓ Migration, invasion, c-MET	BRAF-mutated cell lines		[165]
	↓ Invasion, MMP-9	B16-BL6		[166]
	↓ Lung metastasis, VCAM1		C57BL/6N mice injected with B16- BL6 cells in lateral tail vein	[163]
	↓ Liver metastasis		B16M-F10 cells intravenously injected in C57BL/6J mice	[167]
Resveratrol	↓ Migration, invasion ↓ pAKT	B16F10		[170]
	↓ β-catenin and MITF nuclear translocation ↓ MMP-9	B16		[171]
	↓ MMP-1	Lu1205		[172]
	↓ Lung metastasis		B16-BL6 injected subcutaneously in C57BL6 mice	[170]
	↓ Liver metastasis, adhesion ↓ NF-κB induced inflammation		Intrasplenic inject of B16 cells in C57BL/6J	[173]
Curcumin	↓ Migration, MMPs ↓ pJAK-2, pSTAT-3	A375, B16F10 A375		[175,177]
	↓ Vimentin ↑ E-cadherin	B16		[176]
	↓ Lung metastasis		B16F10 cells subcutaneously injected in C57BL/6 mice	[178]
Silymarin	↓ pMEK1/2, RSK-2, NFκB, STAT3 ↓ β-catenin expression and translocation	SK-MEL-5, SK-MEL-28		[180]
	↓ MMP-2, MMP-9 ↓ Migration, β-catenin	A375, Hs294t, MEL-1241		[181]
Lupeol	↓ β-catenin, MITF, cyclin D1	Mel 928, Mel 1241		[183]
	↓ Motility, migration ↑ Actin depolymerization	B16 2F2		[184]
	↓ Metastasis		Clinical trial on canines with malignant melanoma	[185]
Genistein	↓ MMP-2, MMP-9	518A2		[161]
	↓ Liver metastasis		C57BL/6J mice subcutaneously injected with B164A5 cells	[187]