Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

Table 1

In vitro effects of ginger and its constituents against various GI cancer models.

Cancer	Effects	Reference
Liver
HepG2	Induce apoptosis by activation of caspase-3	[13]
Liver microsomes	Inhibit CYP450, 1-aminobenzotriazole, and aldo-keto reductase; Prevent the formation of M14 and M15 and 18β-glycyrrhetinic acid	[14]
SMMC-7721	Inhibit the phosphorylation of eIF2α and triggered apoptosis	[15]
HeoG2	Release cathepsin D and subsequently cytochrome c; Induce apoptosis and intracellular ROS generation and reduced glutathione	[16]
PC12	Inhibit xanthine oxidase and H2O2-induced damage	[17]
HepG2/Hep3B	Decrease the MMP-9 activity and increase the TIMP-1 expression; Decrease urokinase-type plasminogen activator activity in Hep3B cells	[18]
Hep-2	Dose-dependently suppress cell proliferation	[19]
Mahlavu cells	Activate caspases 3/7 resulting in the DNA fragmentation	[20]
RL34	Activate the Nrf2/ARE-dependent detoxification pathway	[21]
Pancreas
PaCa	Inhibit mRNA expression and protein secretion of angiogenic factors and NF-κB activity	[22]
PANC-1, BxPC	Downregulate of NF-κB signaling and cell survival regulators including COX-2, cyclin D1, survivin, cIAP-1, XIAP, Bcl-2, and MMP-9 and sensitize to gemcitabine	[23]
β-cell (INS-1E)	Induce Ca^2+ signals in the β-cell by activating the TRPV1 channels	[24]
PANC-1	Decrease invasion and metastasis and NF-κB translocation via downregulation of the ERK pathway	[25]
PANC-1	Upregulate p53, p21 proteins level and ROS production	[26]
HPAC, BxPC-3	Decrease cyclin A, Cdk, Rb phosphorylation, and p53 expression	[27]
Gastric Cancer
HUVE-AGS	Inhibit cell proliferation, VEGF expression, and NF-κB activity	[28]
kBZ Jurkat	inhibit COX-2 activation and reduce H. pylori-induced inflammation	[29]
HGC/AGS/and KATO III	Inhibit TRAIL-induced NF-κB activation, cIAP1 expression; Increase TRAIL-induced caspase-3/7 activation	[30]
JB6	Inhibit the growth of all Helicobacter pylori strains	[31]
Colorectal
Caco-2	Inhibit cytochrome P450 enzymes (CYP1A2 and CYP2C8)	[32]
HCT116	Act as antiproliferative agents and enhance the chemotherapeutic effect of 5-FU	[33]
COLO 205	Induce apoptosis, cytochrome c release, caspase activation, and DNA fragmentation; Upregulate the Bax, Fas, and FasL and downregulate Bcl-2 and Bcl-XL proteins	[34]
HCT116	Suppress cyclin D1 expression and induced NAG-1 expression; Inhibit beta-catenin, PKC-epsilon, and GSK-3 beta pathways	[35]
HCT116	Potentiate TRAIL-induced apoptosis and upregulate of TRAIL death receptors (DR-4/-5); Inhibit extracellular signal-regulated kinase 1/2 and p38-MAPK	[36]
Cholangiocarcinoma
CCA (CL-6)	Upregulate MDR1 and MRP3 genes	[37]
KIM-1	Induce programmed cell death through endonuclease activation and induction of p53	[38]
KMC-1	caspase 3 activation, potentiate free-radical formation and accumulation of sphinganine

CYP450, cytochrome P450; eIF2α, eukaryotic initiation factor 2 alpha; ROS, reactive oxygen species; TIMP-1, tissue inhibitor of metalloproteinase 1; Nrf2, nuclear factor (erythroid-derived 2)-like 2; ARE, antioxidant response element; COX-2, cyclooxygenase-2; cIAP-1, cellular inhibitor of apoptosis protein-1; XIAP, X-linked inhibitor of apoptosis protein; MMP-9, matrix metallopeptidase-9; NF-κB, nuclear factor kappaB; ERKs, extracellular-signal-regulated kinase; Rb, retinoblastoma; VEGF, vascular endothelial growth factor; TRAIL, TNF-related apoptosis-inducing ligand; NAG-1, nonsteroidal anti-inflammatory drug- (NSAID-) activated gene-1; PKC, protein kinase C; GSK-3 beta, glycogen synthase kinase-3 beta; MDR1, multidrug resistance gene-1; MRP3; multidrug resistance protein 3.