Curcumin: recent updates on gastrointestinal cancers

Figures & data

Figure 1. Scheme of therapeutic potentials of curcumin against gastrointestinal cancers.

Table 1. Anticancer role and mechanisms of curcumin against gastrointestinal cancers.

Cancer types	Cell lines	Mechanisms	References
Esophagus	TE-1, TE-8, & KY-5	Inhibited cell invasion and proliferation at all stages	Ren et al. (2018)
	KYSE30	Induced apoptotic, cell cycle arrest at G1 phase and cell death	Alibeiki et al. (2017)
	EC109	Decrease AKT level, Induced apoptosis Enhanced the GSK3β, PTEN, and caspase 3 expressions, and signaling pathway of PI3K/AKT	Li et al. (2017)
	Barrett’s esophagus	Lowered cell viability	Lin et al. (2014)
	In-vivo	Induced apoptosis and suppression of STAT3 signaling, Suppressed activation of NF-κB, Increased apoptosis and reduced viability, Reduction in volume of tumor	Y. Liu et al. (2018); Tian et al. (2012)
Gallbladder	GBC-SD	Reduced cell viability & induced apoptosis Activated the appearance of cleaved caspase-3, Regulated ratio of Bax/Bcl-2 Prevented the DNA from replication by blocking the cells in the S phase	Ono et al. (2013)
	HAG-1	At G2/M phase exhibited cell cycle arrest in, Inhibited activation of AKT Mammalian target rapamycin reduction (mTOR) along with elF4E-binding protein-1 (4E-BP1) and S6 kinase-1 (S6K1) down streaming Lowered Bcl-2 function, increased the MAP (mitogen-activated protein) kinase activity, and lowered phosphorylation of anti-apoptotic Bcl-2 levels	T. Y. Liu et al. (2013)
Cont …	In-vivo	Increased expression of SNORA21 inhibited the tumorgenesis	Qin et al. (2019)
Liver	HepG2 & HepG2TT	Suppressed proliferation, invasion, and metastasis induce apoptosis Lowered TLR4 levels and intracellular heat shock protein 70(HSP70, eHSP70).	Ren et al. (2018)
	HepG2 & H22	Tumor microvascular density reduction via reduced expression of VEGF Up-regulated the expression of caspases3 protein	Afrin et al. (2017)
	HepG2	Reduction in fibrosis and steatosis, serum aminotransferases concentrations Decreased the pro-inflammatory IFNγ-inducible protein 10, cytokines (interferon (IFN) γ, and interleukin-1β), and hepatic protein expression Lowered toll-like receptor 4 protein expression of, and cytoplasmic translocation of HMGB1 (high mobility group box 1) Attenuated NF-κB (nuclear translocation of nuclear factor kappa B) Inhibited protein expression of glypican-3, vascular endothelial growth factor, and prothrombin	Tork et al. (2016)
	In-vivo	Repressing the invasion, migration, and metastasis, inhibition of cell proliferation by blockage of Wnt/β-catenin pathway, Inhibition of invasion via blockage of TGF-p/EMT signaling pathway. Enhanced inhibition of tumor growth.	Huang et al. (2020); Zhao et al. (2019); Tang et al. (2019)
Pancreatic	Panc-1 and BxPC-3	Regulated cell morphology and the levels of EMT-related genes Downregulated the p-Akt and p-NF-κB levels	Jalde et al. (2018)
	AsPC-1, MIA PaCa-2, and PANC-1	Up-regulated the levels of BAX, cytochrome-C, Bcl-2 down-regulation	Zhu et al. (2018); Le et al. (2018)
	In-vivo	Metastasis inhibition and inhibition of migration of cancer cells, inhibition of cancerous cell growth, induced apoptosis.	Q. Wang et al. (2017); Ning et al. (2016); Bimonte et al. (2013)
Gastric	HGC-27	Lowered cell viability, inhibited migration & invasion Matrix metalloproteinase 2 and collagenase activity downregulation	Dhivya et al. (2017); Haghi et al. (2017)
	BGC-823 and MKN-28	Suppressed the cell viability & caused cell apoptosis Enhanced Bax protein and lowered Bcl-2 protein Enhanced the proteins related to autophagy (Atg7, Atg5-Atg12, and Beclin1)	Alibeiki et al. (2017)
	In-vivo	Reduction of circulating tumor cells, Inhibited liver metastasis of gastric cancer, Decreased level of NF-κB and COX-2 proteins	Gu et al. (2019); D. Yang et al. (2017)
Colon	CT26	Modulated VEGF signaling regulatory miRNAs	Sesarman et al. (2019)
	C26	Showed Th1/Th2 cell axis inhibitory effect on invasion and dysregulation	Ravindranathan et al. (2018)
	In-vivo	Reversion of Oxaliplatin resistance, Attenuation of abnormal proliferation of colon mucosa. Reduction of the tumor growth	Yin et al. (2019); Wu et al. (2019)

Figure 2. Schematic effects of curcumin on esophagus cancer in a xenograft model.

Figure 3. The role of curcumin and 5-FU (fluorouracil) on the inhibition of P65 expression.

Figure 4. Mechanisms of action of curcumin against GI cancers.

Table 2. Synergistic anti-cancer effects of curcumin with other chemical compounds.

Synergistic Combinations	In-vivo/in-vitro	Results	References
Curcumin + ursodeoxycholic acid	In-vivo	Decreased MDA levels and iNOS expression	Gheibi et al. (2019)
Curcumin + prednisolone	In-vivo	Reduction of TNF-α, IL-1β, and IL-6	Yan et al. (2019)
Curcumin + resveratrol	In-vitro	Increased apoptosis, XIAP downregulation	Du et al. (2013)
Curcumin + selenium	In-vivo	Reduction of IL-6	Al-Dossari et al. (2020)
Curcumin + ursolic acid	In-vivo	Inhibition of IL-1β, IL-19 and COX-2	Tremmel et al. (2019)
Curcumin + piperine	In-vivo	Suppression of cytokines (TNF-α and IL-1β)	Neyrinck et al. (2013)
Curcumin + piperine	In-vitro	Inhibition of osteo-clastogenesis	Martins et al. (2015)
Curcumin + paclitaxel	In-vivo	Reduction in EGFR signaling and glycogen synthase kinase-3	M. Zhou et al. (2015)
Curcumin + flavocoxid	In-vitro	Reduced IL-1β of NF-κβ and activation of transcription-3 mRNA expression	D’Ascola et al. (2019)
Curcumin + boswellic acid	In-vivo	Slight reduction in TNF-α and IL-6 cytokines	Khayyal et al. (2018)
Curcumin + irbesartan	In-vivo	Reduction in levels of IL-6 and TNF-α	Khaled & Mahfouz (2010)

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