Anti-proliferative effects of polyphenols from pomegranate rind (Punica granatum L.) on EJ bladder cancer cells via regulation of p53/miR-34a axis

Phytother Res. 2015 Mar;29(3):415-22. doi: 10.1002/ptr.5267. Epub 2015 Jan 8.

Abstract

miRNAs and their validated miRNA targets appear as novel effectors in biological activities of plant polyphenols; however, limited information is available on miR-34a mediated cytotoxicity of pomegranate rind polyphenols in cancer cell lines. For this purpose, cell viability assay, Realtime quantitative PCR for mRNA quantification, western blot for essential protein expression, p53 silencing by shRNA and miR-34a knockdown were performed in the present study. EJ cell treatment with 100 µg (GAE)/mL PRE for 48 h evoked poor cell viability and caspase-dependent pro-apoptosis appearance. PRE also elevated p53 protein and triggered miR-34a expression. The c-Myc and CD44 were confirmed as direct targets of miR-34a in EJ cell apoptosis induced by PRE. Our results provide sufficient evidence that polyphenols in PRE can be potential molecular clusters to suppress bladder cancer cell EJ proliferation via p53/miR-34a axis.

Keywords: anti-proliferative effects; miR-34a; p53; pomegranate rind.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival
  • Epithelial Cells / drug effects
  • Fruit / chemistry
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Hyaluronan Receptors / metabolism
  • Lythraceae / chemistry*
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Polyphenols / pharmacology*
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Small Interfering
  • Rats
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Hyaluronan Receptors
  • MIRN34 microRNA, human
  • MicroRNAs
  • Polyphenols
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53