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

Table 1 Chemopreventive activities of urolithin A against colorectal cancer

Cell line	Mechanism	Ref.
SW620	↓Proliferation, MMP-9 activity	Zhao et al[21]
	↑Autophagy, LC3
	G2/M arrest
	↑Apoptosis, necrosis
HT-29	↓Proliferation	Cho et al[22]
	↑Apoptosis, necrosis
	G2/M arrest
	↑p21 expression
	↓MMP, ↑caspase 8 and 9 activity
HT-29	↓Proliferation	Kasimsetty et al[23]
	↓G0/G1 ↑G2/M, G0
	↓CYP1 activity
	↑Apoptosis, caspase-3 like activity
HT-29	↓Proliferation	Tortora et al[24]
Caco-2	CYP1A1, UGT1A10	González-Sarrías et al[25]
	CYP1A1 activity
1Caco-2, HT-29, SW480	↓Proliferation	González-Sarrías et al[26]
	S arrest (SW480, Caco-2)
	G2/M arrest
	Gene expression in Caco-2:
	↑ABCG2, TP53, c-MYC, CDKN1A, BIRC5
	Gene expression in SW480:
	↑c-MYC, CDKN1A, BIRC5, CASP3, EGFR
	↓CTNNB1
	Gene expression in HT-29:
	↑CDKN1A
Caco-2, HT-29, SW480	↓Proliferation	González-Sarrías et al[27]
	G2/M (Caco-2, SW480, HT-29)
	S (SW480, HT-29) arrest
HCT-116, Caco-2, HT-29	↓Colony formation	Giménez-Bastida et al[28]
	G2/M arrest (Caco-2, HCT-116)
	↑Senescence-associated β–galactosidase activity (HCT-116)
	↑p53 and p21Cip1/Waf1 expression (HCT-116)
1CSCs (Caco-2 and primary human colon tumor cells)	Caco-2:	Núñez-Sánchez et al[29]
	↓Colonosphere number
	↓ALDHhigh cells
	Primary human colon tumor cells:
	↓Colonosphere number
	↓Colonosphere size
	↓ALDHhigh cells
HCT116	↓Cell growth	Norden et al[32]
	↑p53, p21, TIGAR expression
	↑p53, p21, TIGAR expression
Caco-2, HT-29, SW480	↓Proliferation	González-Sarrías et al[33]
	↑5-FU- and 5’-DFCR-induced cytotoxicity
	G2/M arrest (Caco-2, SW480)
	↑Caspase 9 activity (Caco-2)
Caco-2	NS cell vitality	Kojadinovic et al[36]
	↓ROS
	↓CAT activity
	NS SOD and GPx activity
Caco-2	↓Proliferation	González-Sarrías et al[37]
	Kinase signaling pathway gene expression: ↓FGFR2, ↑DUSP6, c-MYC, Fos, CD44
Human tissue samples /pomegranate extract	↓CD44, CTNNB1 CDKN1A, EGFR, TYMS	Nuñez-Sánchez et al[29,38]

¹mixture containing urolithin A. 5-DFCR: 5-deoxy-5-fluorocytidine; 5′DFUR: 5-deoxy-5-fluorouridine; ALDH: Aldehyde dehydrogenase; CAT: Catalase; CYP450: Cytochrome P450; GPx: Glutathione peroxidase; LC3: GFP-microtubule-associated protein 1 light chain 3; MMP-9: Matrix metalloproteinase-9; NS: Non significant change; ROS: Reactive oxygen species; SOD: Superoxide dismutase; TIGAR: TP53 induced glycolysis regulatory phosphatase.