Extracellular Histone Promotes Prostate Cancer Migration and Epithelial-Mesenchymal Transition through NF-κB-Mediated Inflammatory Responses

Chemotherapy. 2019;64(4):177-186. doi: 10.1159/000504247. Epub 2020 Jan 14.

Abstract

Introduction: This study aims to explore the relationship betweenextracellular histone and prostate cancer and its mechanism.

Methods: Migration of prostate cancer cells was detected by Transwell. Inflammatory factor expression was investigated by ELISA. Epithelial-mesenchymal transition and expression of NF-κB pathway-related proteins were investigated using Western blotting.

Results: Under the induction of extracellular histones, the migration rate of prostate cancer cells and the levels of IL-1β, TNF-α, and IL-6 were notably enhanced. Then, expression of E-cadherin was significantly down-regulated, while levels of N-cadherin, vimentin, β-catenin, Snail, p-p65 and p-IκBα were significantly up-regulated, which was reversed by PDTC (pyrrolidine dithiocarbamate).

Conclusion: Extracellular histone significantly promotes the progression of prostate cancer cells via NF-κB pathway-mediated inflammatory responses, which may serve as a novel target for treating prostate cancer.

Keywords: Epithelial-mesenchymal transition; Extracellular histone; Migration; NF-κB pathway; Prostate cancer.

MeSH terms

  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Histones / pharmacology*
  • Humans
  • Male
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism
  • Up-Regulation / drug effects

Substances

  • Cadherins
  • Histones
  • NF-kappa B
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha