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Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

Tamires Cunha Almeida1, Camila Chaves Coelho Guerra2, Bárbara Letícia Gonçalves De Assis1

  • 1Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.

Environmental and Molecular Mutagenesis
|May 17, 2019
PubMed

Insights

Resveratrol exhibits antitumor effects in bladder cancer cells, with its mechanism influenced by TP53 gene status. Wild-type TP53 cells showed increased apoptosis, while mutated cells experienced cell cycle arrest.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Resveratrol, a grape-derived polyphenol, shows potential antitumor activity across various cancers.
  • Its antiproliferative effects in bladder cancer are known, but mechanisms remain unclear.
  • Understanding these mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the antitumor activity of resveratrol in bladder tumor cells.
  • To elucidate the mechanisms of action based on TP53 gene status (wild-type vs. mutated).
  • To evaluate resveratrol's impact on cell proliferation, apoptosis, cell cycle, and specific gene expression.

Main Methods:

  • Assessed resveratrol's effects on cell proliferation, clonogenic survival, and morphology.
  • Analyzed cell cycle progression, apoptosis rates, and genotoxicity.
  • Utilized immunocytochemistry for p53 and PCNA, and quantified gene expression of AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1.

Main Results:

  • Resveratrol reduced proliferation and induced DNA damage in all tested bladder cancer cell lines.
  • TP53 wild-type cells exhibited higher resistance to resveratrol's long-term effects but increased apoptosis with AKT, mTOR, and SRC downregulation.
  • TP53 mutated cells showed S-phase arrest, PLK1 downregulation, and modulation of the HOXB3/RASSF1A pathway.

Conclusions:

  • Resveratrol demonstrates antiproliferative activity in bladder tumor cells.
  • The specific mechanisms of resveratrol's action are significantly dependent on the TP53 gene's mutational status.
  • Findings highlight the importance of TP53 status in predicting response to resveratrol therapy.
Keywords:
TP53 genebladder cancerresveratrol

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