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Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells

Joana Liberal1,2, Anália Carmo3,4, Célia Gomes5,6

  • 1Escola Superior de Saúde Dr. Lopes Dias, Instituto Politécnico de Castelo Branco, Campus da Talagueira, Avenida do Empresário, 6000-767, Castelo Branco, Portugal. joanaliberal@gmail.com.

Investigational New Drugs
|June 21, 2017
PubMed

Insights

Urolithins, metabolites of ellagitannins, show anticancer potential. Urolithin A effectively inhibited bladder cancer cell growth by inducing cell cycle arrest and apoptosis, suggesting its therapeutic promise.

Area of Science:

  • * Biochemistry and Molecular Biology
  • * Cancer Research
  • * Nutraceuticals and Natural Products

Background:

  • * Ellagitannins are natural compounds with potential health benefits, but their low bioavailability necessitates understanding the role of their metabolites.
  • * Urolithins, derived from ellagitannins, are increasingly recognized for their chemopreventive and chemotherapeutic properties.
  • * Further research is needed to evaluate the selectivity and mechanisms of action of urolithins against various cancer types.

Purpose of the Study:

  • * To investigate the antiproliferative effects of urolithins A, B, and C, and ellagic acid on diverse human tumor cell lines.
  • * To identify the most sensitive cancer cell lines to urolithin treatment.
  • * To elucidate the cellular mechanisms underlying the activity of the most potent urolithin in susceptible cancer cells.

Main Methods:

  • * Cell viability assays were performed to determine the half-maximal inhibitory concentrations (IC50) of urolithins and ellagic acid.
  • * Flow cytometry was used to analyze cell cycle distribution and apoptosis.
  • * Western blotting was employed to assess the impact on PI3K/Akt and MAPK signaling pathways.

Main Results:

  • * Significant variability in sensitivity to urolithins was observed across different human tumor cell lines.
  • * Bladder cancer cells (UMUC3) exhibited the highest susceptibility to the tested urolithins.
  • * Urolithin A demonstrated the strongest activity in UMUC3 cells, inducing G2/M cell cycle arrest, promoting apoptosis, and inhibiting PI3K/Akt and MAPK signaling pathways.

Conclusions:

  • * Urolithins possess significant antiproliferative and anticancer potential, with varying efficacy depending on the cell type.
  • * Urolithin A is a particularly potent agent against transitional bladder cancer cells.
  • * The findings support the chemotherapeutic and chemopreventive roles of urolithins, especially urolithin A, in targeting bladder cancer.
Keywords:
ApoptosisCell cycleEllagitanninsIntracellular signaling pathwaysUMUC3Urolithins

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