Table 1.

The molecular mechanisms of PCs in nicotine-induced NSCLC treatment.

Study Type	NSCLC Cell Type	Extract/Compound	Concentrations	Activity	Mechanisms of Action	Reference
In vitro	DMS114	Cranberry presscake	200–300 µmol/L	Anti-proliferative, apoptosis	NA	[40]
In vitro	H460	Cranberry (Vaccinium macrocarpon)	20–80 µg/mL	Anti-proliferative	MMP2, MMP9↓	[41]
In vitro	H460	Cranberry (Vaccinium macrocarpon)	50 µg/mL	Apoptosis, cell cycle arrest	P21, P73, PARP, cytochrome c, caspase3/4/8↑ Bcl-2↓	[42]
In vitro/vivo	A549	Grape seed	100 µg/mL (in vitro) 30 mg PC/kg bodyweight (in vivo)	Inhibition of tumor angiogenesis	MMP2↓	[43]
In vitro/vivo	A549, H1299	Grape seed	60, 80 µg/mL (in vitro) Administration of PCs (0.1%, 0.2%, and 0.5%, bodyweight) (in vivo)	Anti-proliferative, anti-angiogenic, apoptosis	PCNA↓ IGFBP-3↑	[44]
In vitro/vivo	H157, H226, H460, H1299, A549	Grape seed	20, 40, and 60 µg/mL (in vitro) Administration of PCs (0.5%, bodyweight) (in vivo)	Anti-proliferative, apoptosis	COX-2, PGI-2↓	[45]
In vitro	A549, H1299	Grape seed	10, 20, 40, and 60 µg/mL	Anti-migration	NO, L-NAME, MAPK, ERK1/2↓	[46]
In vitro	A549	Grape seed	6 µg/mL	Anti-proliferative, apoptosis	caspase 3, PTGIS/PGI2↑	[47]
In vitro	A549, H1299, H460	Grape seed	20 and 40 µg/mL	Anti-migration	E-cadherin, NOX, p22/p47(phox)↓ N-cadherin, fibronectin, vimentin↑	[48]
In vitro/vivo	A549, H1299	Grape seed	20, 40, and 60 µg/mL (in vitro) 50, 100, and 200 mg PC/kg bodyweight (in vivo)	Apoptosis	G1arrest, Bax, caspases-3/9, Cdki, PARP↑ Bcl-2,Bcl-xl, Cdk2/4/6, cyclins↓	[49]
In vitro/vivo	A549	Grape seed	45 µg/mL (in vitro) 112 mg PC/kg bodyweight (in vivo)	Anti-proliferative, anti-invasive	CDKN1A, p21↑, miR-106b↓	[50]
In vitro	A549	Cinnamomi Cortex	2.5 µg/mL	Inhibition of cell viability and proliferation	Nrf2↓	[51]
In vitro	A549	Cinnamomi Cortex	10 µg/mL	Inhibition of cell proliferation	Nrf2, IGF-1R↓	[52]
In vitro	A549	Cinnamomi Cortex	12.5, 25, 50, and 100 µg/mL	Anti-metastatic	TGF-β, snail, E-cadherin, smad2↓	[53]
In vitro	A549	PCs	≥100 mg/L	Inhibition of cell viability	ROS, MDA, Nrf2↓ HO-1, NQO1, TXNRD1, glutathione, catalase, superoxide dismutase↑	[54]
In vitro	A549	PCs	12.5, 25, 50, 100, and 200 µM	Inhibition of cell viability and proliferation, apoptosis, cell cycle arrest	N-cadherin, vimentin, Bcl-2, MMP2/9, JAK2/STAT3↓, Bax↑	[55]
In vitro	A549	Green tea leaf	1, 5, 10, 20 µM	Anti-proliferative, apoptosis, cell cycle arrest	P21, P53, Fas/sFasL, Fas/APO-1↑	[56]
In vitro	A549	Myrica rubra	0.5, 2.5, 5, and 10 µM	Anti-proliferative, apoptosis, cell cycle arrest	Fas/APO-1, P21/WAF1, P53, Fas/sFasL↑	[57]
In vitro	A549, H460	Rhododendron formosanum	125, 150, and 175 µM	Autophagy	Akt/mTOR↓	[58]

(↑) increase; (↓) decrease; NA: not mentioned.