Punica granatum Extract Inhibits Bladder Cancer Cell Viability, Invasion and Migration through Down-Regulation of HOXD10 Signalling Pathway

Dokl Biochem Biophys. 2021 Mar;497(1):130-136. doi: 10.1134/S1607672921020162. Epub 2021 Apr 24.

Abstract

The present study investigated Punica granatum extract (PGE) as potential proliferation inhibitory agent for bladder cancer cells and elucidated the possible mechanism. PGE reduced viabilities of HT-1197 and RT4 cells in concentration-based manner at 72 h. Colony forming potential of HT-1197 and RT4 cells was also significantly (p < 0.05) inhibited on exposure to 2 and 12 mg/mL PGE. Exposure to 12 mg/mL PGE for 72 h significantly (p < 0.05) decreased miR‑10b expression and suppressed migration potential of HT-1197 and RT4 cells. In PGE exposed HT-1197 and RT4 cells, invasiveness was reduced to 30.25 and 33.47%, respectively. PGE treatment of HT-1197 and RT4 cells caused a significant (p < 0.05) elevation in HOXD10 protein and mRNA levels compared to control. The miR‑10b mimic transfection in HT-1197 and RT4 cells reversed inhibitory effect of PGE on cell viability. Thus, PGE exhibited cytotoxicity and anti-invasive effect on HT-1197 and RT4 cells through targeting miR‑10b and up-regulation of HOXD10 expression. Thus, PGE may be developed as therapeutic agent for treatment of bladder cancer.

Keywords: Punica granatum extract; bladder cancer; migration; oncogenes; viability.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects*
  • Down-Regulation / drug effects
  • Homeodomain Proteins / metabolism*
  • Humans
  • Neoplasm Invasiveness
  • Plant Extracts / pharmacology*
  • Pomegranate / chemistry*
  • Signal Transduction / drug effects*
  • Time Factors
  • Transcription Factors / metabolism*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • Homeodomain Proteins
  • Plant Extracts
  • Transcription Factors
  • HOXD10 protein, human