title: In vitro antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells.
abstract: The intestinal metabolites of ellagic acid (EA), urolithins are known to effectively inhibit cancer cell proliferation. This study investigates antiproliferative and antioxidant effects of urolithin A (UA) on cell survival of the HepG2 hepatic carcinomas cell line. The antiproliferative effects of UA (0-500 μM) on HepG2 cells were determined using a CCK assay following 12-36 h exposure. Effects on β-catenin and other factors of expression were assessed by using real-time PCR and Western blot. We found that UA showed potent antiproliferative activity on HepG2 cells. When cell death was induced by UA, it was found that the expression of β-catenin, c-Myc and Cyclin D1 were decreased and TCF/LEF transcriptional activation was notably down-regulated. UA also increased protein expression of p53, p38-MAPK and caspase-3, but suppressed expression of NF-κB p65 and other inflammatory mediators. Furthermore, the antioxidant assay afforded by UA and EA treatments was associated with decreases in intracellular ROS levels, and increases in intracellular SOD and GSH-Px activity. These results suggested that UA could inhibit cell proliferation and reduce oxidative stress status in liver cancer, thus acting as a viably effective constituent for HCC prevention and treatment.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China.
authors.forename: Benhong
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Medical Microbiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, School of Life Science, Wuchang University of Technology, Wuhan 430223, People's Republic of China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Department of Medical Microbiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Qiujin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Medical Microbiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Medical Microbiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, People's Republic of China. Electronic address: zhufan@hotmail.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D004610:Ellagic Acid / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D003374:Coumarins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid
keywords: Hepatocellular carcinomas; NF-κB p65; Urolithin A; p53; β-catenin