Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development

Table 1 Chemopreventive phytochemicals and their actions and targets/mechanisms during the development of esophageal cancer, gastric cancer and colon cancer

	Natural phytochemical	Chemopreventive action	Targets/mechanisms	Ref.
Esophageal cancer	Isothiocyanate	Inhibition of DNA damage	Inhibition of DNA methylation	[17]
		Inhibition of tumorigenesis	Inhibition of cytochrome P450 enzymes activity	[11,18]
	EGCG	Anti-inflammation	Inhibition of phosphorylated ERK1/2, c-Jun and COX-2 expressions	[30]
			Decreased COX-2 expression and PGE2 production	[32]
		Growth inhibition	Inhibition of EGFR phosphorylation	[31]
		Induction of cell cycle arrest	Inhibition of cyclin D1	[32]
		DNA damage	Inhibition of DNA methyltransferase activity	[29]
	Curcumin	Antioxidant	Induction of SOD-1	[46]
		Anti-inflammation	Inhibition of COX-2	[46]
			Inhibition of NF-κB activity	[50-52]
			Inhibition of IL-8 mRNA expression	[52]
		Apoptosis and cell cycle arrest	Inhibition of Notch signaling	[57]
Gastric cancer	Curcumin	Chemoresistance	Downregulation of NF-κB	[61]
			Induction of apoptotic genes Bcl-2 and Bcl-xL	[61]
		Suppression of cell proliferation and invasion	Downregulation of EGFR-PAK1	[62]
			Reduction of cyclin D1 expression	[62]
	Resveratrol	Inhibition of cell cycle progression	Inhibition of PKC	[72,73]
			MEK1/2-ERK1/2-c-Jun	[74]
		Induction of apoptosis	Reduction in Bcl-2, enhancing Bax gene	[76,77]
	Sulforaphane	Protection against oxidative stress	Stimulation of Nrf2	[78-80]
			Enhancement of GST and glutathione levels	[78,81]
		Anti-bacterial activity	Decrease in gastric bacterial colonization	[82]
			Reduction in the expression of TNF-α and IL-1β	[82]
Colon cancer	Curcumin	Growth inhibition	EGFR/IGFR	[102]
			ERK/Egr-1/EGFR	[87,96]
		Suppression of tumorigenesis	AMPK-COX-2	[101]
			Wnt/β-catenin	[102,106]
	Resveratrol	Anti-proliferation Apoptosis	IGF-1, p53	[108]
			PPP-FAK signaling	[109]
		Apoptosis growth inhibition	AMPK	[110]

ERK: Extracellular-signal-regulated kinase; COX-2: Cyclooxygenase-2; PGE₂: Prostaglandin E2; EGFR: Epidermal growth factor receptor; EGCG: Epigallocatechin gallate; SOD: Superoxide dismutase; NF-κB: Nuclear factor κB; IL-8: Interleukin-8; PKC: Protein kinase C; MEK: Mitogen-activated protein kinase; Bcl-2: B-cell lymphoma 2; GST: Glutathione S-transferase; TNF: Tumor necrosis factor; IGFR: Insulin-like growth factor receptor; PPP: Pentose phosphate pathway; FAK: Focal adhesion kinase; AMPK: Adenosine monophosphate-activated potein kinase.