In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells

Food Chem Toxicol. 2013 Sep;59:428-37. doi: 10.1016/j.fct.2013.06.025. Epub 2013 Jun 26.


Urolithins were the metabolites of ellagic acid by intestinal flora in gastrointestinal tract. In previous research, it was found that urolithins could mainly inhibit prostate cancer and colon cancer cell growth. However, there is no report about bladder cancer therapy of urolithins. In this paper, three urolithin-type compounds (urolithin A, urolithin B, 8-OMe-urolithin A) and ellagic acid were evaluated for antiproliferative activity in vitro against human bladder cancer cell lines T24. The IC₅₀ values for T24 cell inhibition were 43.9, 35.2, 46.3 and 33.7 μM for urolithin A, urolithin B, 8-OMe-urolithin A and ellagic acid, respectively. After the administration of urolithins and ellagic acid, we found these compounds could increase mRNA and protein expression of Phospho-p38 MAPK, and decrease mRNA and protein expression of MEKK1 and Phospho-c-Jun in T24 cells. Caspase-3 was also activated and PPAR-γ protein expression increased in drug-induced apoptosis. And what's more, the antioxidant assay afforded by three urolithins and EA treatments were associated with decreases in the intracellular ROS and MDA levels, and increased SOD activity in H₂O₂-treated T24 cells. The results suggested that these compounds could inhibit cell proliferation by p38-MAPK and/or c-Jun medicated caspase-3 activation and reduce the oxidative stress status in bladder cancer.

Keywords: Antioxidant; Antiproliferative; Apoptosis; Ellagic acid; Urolithin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / chemistry
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colon / microbiology
  • Coumarins / metabolism
  • Coumarins / pharmacology*
  • Ellagic Acid / metabolism
  • Ellagic Acid / pharmacology*
  • Enterobacteriaceae / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Lipid Peroxidation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Methylation
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oxidative Stress / drug effects
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / metabolism
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Coumarins
  • Neoplasm Proteins
  • PPAR gamma
  • Reactive Oxygen Species
  • 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
  • Ellagic Acid
  • p38 Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3