Mechanisms of resveratrol in the prevention and treatment of gastrointestinal cancer

Table 1 Effect and targets/mechanisms of resveratrol in gastric cancer and colorectal cancer

	Effect	Cell or animal model	Proposed targets/mechanisms	Ref.
Gastric cancer	Anti-H. pylori	MKN-45 cells	Inhibition of IL-8 secretion, inhibition of ROS generation	[27]
		Mice	Downregulation of IL-8 and iNOS, inhibition of NF-κB activity, activation of the Nrf2/HO-1 pathway	[30]
	Anti-proliferation	KATO-III cells	Inhibition of PKC activity	[34]
		ACS cells	The MEK1/2-ERK1/2- c-Jun signaling pathway	[37]
		SNU-1 cells	The PTEN/ PI3K/Akt signaling pathway	[25]
		MGC803 cells	The PI3K/Akt signaling pathway	[38]
		MGC-803 cells	Downregulation of β-catenin, c-myc, and cyclin D1, inhibition of the Wnt/β-catenin pathway	[39]
	Inhibition of invasion and metastasis	SGC7901 cells	Inhibition of the Hh signaling pathway and EMT	[41]
		SGC7901 cells	Inhibition of the Raf/MAPK signaling pathway	[44]
		BGC823 cells	Inhibition of MALAT1	[42]
	Induction of apoptosis and senescence	SGC7901 cells	Downregulation of survivin	[45]
		SGC-7901 cells	Increase of ROS	[46]
		AGS, BGC-823 and SGC-7901 cells	Downregulation of the senescence pathways such as cyclin D1, CDK 6 and CDK4, p16 and p21	[47]
		Nude mice	Downregulation of anti-apoptotic gene bcl-2, up-regulation of the pro-apoptotic gene bax	[52]
		SGC 7901 cells	Upregulation of bax, cleaved caspase 3 and cleaved caspase 8, downregulation of bcl-2, inhibition of NF-κB activity	[53]
		SGC-7901 cells	Activation of caspase-3 and pro-caspase 9 was downregulated, the expression ratio of bax/bcl-2 was increased	[54]
		SNU-1 cells and KATO-III cells	Upregulation of both Fas and Fas-Lin SNU-1 cells, upregulation of Fas-L in KATO-III cells	[56]
		SNU-1, KATO- and RF-1 cells	SNU-1 cells: Upregulation of p53, downregulation of surviving; AGS cells: Upregulation of p53, stimulation of caspase 3 and cytochrome C oxidase activities; KATO-III cells (not expressing p53): Stimulation of caspase 3 and cytochrome C oxidase activities	[57]
		SNU-1 cells	Upregulation of p53 expression	[58]
	MDR	SGC7901/DOX	PTEN/Akt signaling pathway	[62]
		RDB and RNOV	In RDB cells, Res reduced the expression level of all analyzed genes, so were results at the protein level obtained for P-gp and TXN. In turn, in the RNOV cell line, Res reduced TXN expression at mRNA and protein levels	[63]
Colorectal cancer	Anti-inflammatory	HCA-7 cancer cells	Downregulation of COX-2 III	[67]
		Dextran Sulfate Sodium (DSS) mouse model of colitis	Decrease of CD3+ T cells, downregulation of p53	[68]
		Caco-2 and SW480 cells	Inhibition of iNOS, decrease of NO production, inhibition of NF-κB activity	[70]
		Mice	Downregulation of Nrf2	[72]
	Inhibit oxidative stress	Wistar male rats	Increase of the enzymic and non-enzymic antioxidant status	[74]
	Anti-proliferation	CaCo-2 cells	Inhibition of ODC expression	[75]
		SW480 cells	Modulation of cyclin and CDK activities	[76]
		HT-29 and WiDr cells	Downregulation of telomerase activity	[78]
		HT-29 cells	Inhibition of IGF-1R and the downstream Akt/Wnt signaling pathway	[80]
		HCT116 cells	Downregulation the PTEN/PI3K/Akt and Wnt/β-catenin signaling	[81]
	Induce apoptosis	HCT116 cells	Induction of bax, activation of caspases 3 and 9	[83]
		HT-29 cells	Production of O2-•, increase of mitochondrial ROS production	[84]
		SW480 cells	Redistribution of Fas	[85]
		HT-29 cells	Lysosomal cathepsin D demonstrated upstream of cytosolic caspase activation	[86]
		HT-29 cells	ROS-triggered autophagy, decrease of cleavage of casapse-8 and caspase-3	[87]
		HT- 29 cells	The PKC- ERK1/2 signaling pathway	[90]
	Inhibit invasion and metastasis	LoVo and HCT116 cells	Downregulation of MALAT1, decrease of β-catenin attenuation of Wnt/β-catenin signaling	[91]
		HCT116 cells	ERK and p38-dependent pathways, downregulation of TCF4	[93]
		HCT116 and SNU81 colon cancer cells	Increase of TTP expression	[94]
		HCT116 cells	Suppression of NF-κB signaling pathway	[98]
		HCT116, RKO and SW480 cells	Decrease of TNF-β/TNF-βR-induced EMT, suppression of NF-βB and FAK	[99]
	Inhibition of angiogenesis	Caco2 cell and HCT116 cells	Reduction of VEGF level	[105]
	Reversion of MDR	5-FU-sensitive HCT-116 cells	Decrease of the levels of POL-β, POLH, FEN1and DDB2	[106]
		5-FU chemoresistance-derived clones HCT116R cells	Upregulation of intercellular junctions and downregulation of NF-κB pathway	[107]
		HCT116R cells	Suppression of tumor-promoting factors (NF-κB, MMP-9, CXCR4) activity and EMT factors	[108]
		CIS-resistant HCT 116 cells	Increase in the early apoptosis fraction and enhance the subsequent apoptotic effects of CIS	[109]
		HCT116/LOHP	Downregulation of mRNA and P-gp/MDR1 and MDR1 promoter activity	[110]

IL: Interleukin; ROS: Reactive oxygen species; NO: Nitric oxide; iNOS: Inducible nitric oxide synthase; Nrf2: Nuclear factor erythroid 2-related factor 2; EMT: Epithelial-mesenchymal transition; Hh: Hedgehog; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; CIS: Cisplatin; NO: Nitric oxide; MDR1: Multi-drug resistance protein 1.