Potential of the ellagic acid-derived gut microbiota metabolite – Urolithin A in gastrointestinal protection

Table 3 Chemopreventive activities of urolithin A against other cancers of the alimentary tract

Cell line/model	Mechanism	Ref.
Liver
HepG2	↓Cell survival	Wang et al[50]
	↓Wnt/β-catenin signalling; β-catenin
	↓c-MYc, cyclin D1, phospo-c-Jun
	↓IL-6, IL-1β, NF-κβ, Cox-2, iNOS
	↑TP53, BAX, PUMA, NOXA, p53, phosphor-p53
	↑Caspase-3, phospho-p38
	↓H2O2-induced ROS, MDA level
	↑SOD level, GPx activity in H2O2-induced oxidative stress
HepG2.2.15	↓Cell proliferation	Qiu et al[51]
	↓Bcl-2
	↑Cleaved caspase-3, Bax
	↓Lin28a, Zcchc11, Sp-1
	↑Let-7a
	↓HMGA2, K-ras
	↓Invasive cell number
Cultured rat hepatocytes/t-BHT	↓Cytotoxicity	Olennikov et al[55]
	↓LDH, MDA level
Pancreas
The human PDAC cell lines (MiaPaCa2, PANC1, AsPC1, CFPAC1, Capan1, Capan2, SW1990, HPAC, BxPC3)	↓Cell proliferation, migration, apoptosis	Totiger et al[58]
	↓pAKT (T308), p70S6K (T421/S424), PDK1, pGSK3β, p4E-BP1
PDAC xenografts in mice	↓Tumor volume	Totiger et al[58]
	↓pAKT (T308), p70S6K (T421/S424)
	↓Ki67
	↑Cleaved caspase-3
PKT mice	↓Tumor weight	Totiger et al[58]
	↑Survival
	↓pAKT (T308), p70S6K (T421/S424)
	↓Ki67
	↑Cleaved caspase-3
	↓F4/80-, Fox-P3, CD3- positive cells
Esophagus
BE patients/LBR intervention	↑GST-pi level in BE biopsies	Kresty et al[59]

BE: Barrett’s esophagus; Bcl-2: B-cell lymphoma 2; GST: Glutathione S-transferase; HMG2: High-mobility group AT-hook 2, MDA: Malondialdehyde; t-BHP: tert-butyl hydroperoxide; LBR: Lyophilized black raspberries; LDH: Lactate dehydrogenase; MMP: Matrix metalloproteinase; PDAC: Pancreatic ductal adenocarcinoma; ROS: Reactive oxygen species; SOD: Superoxide dismutase; HMGA2: High mobility group AT-hook 2.