Induction of CYP1A1 only within the colon of rats incubated with Uro-A and Uro-B dissolved in PBS and not in sunflower oil (49). The in situ outcomes points to a essential impact from the dissolving media within the activities in the urolithins. One more study also confirmed the potential inhibitory effects of quite a few urolithins metabolites on CYP1. In accordance with Kasimsetty et al. (70). Uro-A (IC50 , 56.7 two.6 ), Uro-B (IC50 , 58.six four.two ), and Uro-C (IC50 , 74.eight 2.29 ) exerted dosedependent inhibition of TCDD-induced CYP1 enzymes on HT29 cells. These metabolites, such as Uro-D, induced a dose and time-dependent antiproliferative action on HT-29 cells with IC50 values within the selection of 31678 . These weak albeit antiproliferative potentials are certain to cancer cells only and are linked with apoptosis induction (70). Urolithin A has been showed to exert a synergistic action with oxaliplatin on colon cancer cells. Oxaliplatin is a regular FGFR Purity & Documentation chemotherapeutic drug applied for therapy against colon cancer. Urolithin A in a time and dose-dependent manner (39.2 , 48 h, and 19.6 , 72 h) CD38 MedChemExpress inhibited the growth of HCT116 cells and halted cell cycle progression at the G2 /M phase. The UroA growth inhibitory impact on HCT 116 cells is p53-dependent at a low dose and p53 independent at a high dose. Uro- A also showed p53-dependent synergistic action with oxaliplatin as evidenced in the reported combinatorial indices (CI) of 1 (58). A CI worth 1 denotes synergism, values 1 indicates antagonism and values = 1 denotes an addictive effect (117). These study data imply that urolithin could help oxaliplatin chemotherapy against colon cancer. Moreover, cancer cellsFrontiers in Nutrition | www.frontiersin.orgJune 2021 | Volume 8 | ArticleAl-Harbi et al.Urolithins in Cancer Preventionrely on aerobic glycolysis for glucose metabolism. This metabolic reprogramming from oxidative phosphorylation to glycolysis has been recommended to market tumor cell growth and malignancy (118) and recognized as an emerging hallmark of cancer (104). An elevated aerobic lactic acid production by means of glycolysis is linked with drug resistance in LoVo colon carcinoma cells (119). Therefore, an interruption of cellular bioenergetics in tumor cells can sensitize the cell to chemotherapy and inhibit tumor development by way of energy depletion. Working with extracellular flux analysis, Norden and Heiss (58), showed that Uro- A influenced cellular bioenergetics in HCT 116 cells within a p53dependent manner through a reduction in glycolytic prospective. This reduced glycolytic possible is related with all the induction of TP53-induced glycolytic regulatory phosphatase (TIGAR) in WT HCT116 cells. TIGAR is actually a adverse regulator of glycolysis. Its overexpression leads to a lower in cellular fructose-2,6bisphosphate levels, resulting inside the inhibition of glycolysis (120). Hence, this study points to a further Uro-A antiploriferative potentials against cancer cells. Uro-A’s combinational therapy with 5-Fluorouracil (5-FU) and 5-deoxy-5-fluorouridine (5 DFUR) has been examined on colon cancer cell lines. The five DFUR is often a pro-drug as well as an intermediate of 5-FU. The co-treatment of 5-FU with Uro-A enhanced the sensitivity of 5-FU in Caco-2 (1.2 and 2.4-fold), SW480 (1.six and two.4-fold), and in HT-29 cells (1.three and 1.7-fold) within the presence of ten and 20 , 72 h of Uro-A, respectively. The same enhanced sensitivity was observed when Uro-A at a nontoxic concentration of ten or 20 was cotreated with 5 DFUR in Caco-2 (1.3 and.