Table 5.

Chemopreventive diet phytochemicals regulate melanoma metastasis and related protein expression/activity.

Phytochemicals	Origin	Cell or animal models	Effect	Mechanism
Berberine	Coptis chinensis	A375 and Hs294 in vitro	Cell invasion↓, TPA-induced cell migration↓	COX-2↓, PGE2↓, EP2↓, EP4↓, NF-κb↓ [226]
		A375 and B16F10 in vitro, B16F10 experimental pulmonary metastasis in mice	Cell invasion and migration↓, lung metastasis↓	AMPK↑, ERK↓, COX-2↓ [227]
Proanthocyanidins (PC)	Grape	A375 and Hs294t in vitro, TPA-stimulated A375 in vitro, A375 experimental pulmonary metastasis in mice	Cell invasion and migration↓, lung metastasis↓	COX-2↓, EP2↓, EP4↓, NF-κb↓, epithelial biomarkers↑ (E-cadherin, cytokeratin), mesenchymal biomarkers↓ (vimentin, fibronectin and N-cadherin) [228]
Anthocyanins	Mulberry	B16F1 in vitro, B16F1 spontaneous metastatic model in mice	Cell invasion and migration↓, lung and liver metastasis↓	MMP-2/9↓, Ras↓, Akt↓, NF-κb↓ [229]
Silymarin	Milk thistle	A375 and Hs294t in vitro	Cell invasion and migration↓	β-catenin↓, MMPs↓ [230]
Quercetin	Fennel, caraway, onion	HGF-stimulated A2058 and A375 in vitro	Cell invasion and migration↓	C-Met↓, Gab1↓, FAK↓, PAK↓ [231]
		A375 and A2058 in vitro, B16F10 experimental pulmonary metastasis in mice	Cell invasion and migration↓, lung metastasis↓	STAT3↓, MMP-2↓, MMP-9↓, VEGF↓ [232]
Apigenin	Caraway	B16F10 experimental pulmonary metastasis in mice	Lung metastasis↓	STAT3↓, MMP-2↓, MMP-9↓, VEGF↓ and Twist1↓ [233]
EGCG	Green tea	A375 and Hs294t in vitro	Cell invasion and migration↓	COX-2↓, PGE2↓, EP2↓, EP4↓, epithelial biomarkers↑ (E-cadherin, cytokeratin and desmoglein 2), mesenchymal biomarkers↓ (vimentin, fibronectin and N-cadherin) [234]
		M17 in vitro	Cell migration↓	MMP-2↓, TIMP-2↑, ERk↓ [235]
Capsaicin	Pepper	B16F10 in vitro	Cell migration↓	Akt↓, PI3K↓, Rac1↓ [217]
Resveratrol	Red grape	B16F10 in vitro, B16BL6 experimental pulmonary metastasis in mice	Cell invasion and migration↓, lung metastasis↓	Akt↓ [236]
Pterostilbene	Blueberry	B16MF10 experimental liver metastasis in mice	Metastatic growth to the liver↓	Vascular adhesion molecule 1↓ [237]
Gallic acid	Grape, tea	A375. S2 in vitro	Cell invasion and migration↓	Ras/ERK pathway↓, pathways MMP-2/9↓ [238]
Riboflavin	Animal foods, carrot, tomato	B16F10 in vitro, B16F10 experimental pulmonary metastasis in mice	Cell invasion and migration↓, lung metastasis↓	TIMP↑, MMPs↓, HH pathway↓ [239]
Carnosol	Rosemary	B16F10 in vitro	Cell invasion↓	MMP↓, Akt↓, MAPK↓ NF-κb↓, AP-1↓ [225]
Parthenolide	Feverfew	A375 and WM793 in vitro	Cell invasion and migration↓	NF-κb↓, IL-8↓ and MMP-9↓ [240]
Lipid-soluble extract	Ginseng	B16F10 in vitro, B16F10 experimental pulmonary metastasis in mice	Cell migration↓, lung metastasis↓	MMP-2↓ [241]
Ginsenoside Rg3	Ginseng	B16F10 in vitro	Cell invasion and migration↓	MMP-13↓ [242]
1-Deoxynojirimycin ursolic acid	Mulberry Berries	B16F10 in vitro B16F10 experimental pulmonary metastasis in mice	Cell invasion and migration↓ lung metastasis↓	MMP-2/9↓, TIMP↑, α-mannose↑ [243] focal adhesion pathway (ICAM-1, VCAM-1, E-selectin, P-selectin, integrins)↓ [220]