Piperlongumine inhibits NF-κB activity and attenuates aggressive growth characteristics of prostate cancer cells

Prostate. 2014 Feb;74(2):177-86. doi: 10.1002/pros.22739. Epub 2013 Oct 22.

Abstract

Background: Elevated NF-κB activity has been previously demonstrated in prostate cancer cell lines as hormone-independent or metastatic characteristics develop. We look at the effects of piperlongumine (PL), a biologically active alkaloid/amide present in piper longum plant, on the NF-κB pathway in androgen-independent prostate cancer cells.

Methods: NF-κB activity was evaluated using Luciferase reporter assays and Western blot analysis of p50 and p65 nuclear translocation. IL-6, IL-8, and MMP-9 levels were assessed using ELISA. Cellular adhesion and invasiveness properties of prostate cancer cells treated with PL were also assessed.

Results: NF-κB DNA-binding activity was directly down-regulated with increasing concentrations of PL, along with decreased nuclear translocation of p50 and p65 subunits. Expression of IL-6, IL-8, MMP-9, and ICAM-1 was attenuated, and a decrease of cell-to-matrix adhesion and invasiveness properties of prostate cancer cells were observed.

Conclusions: PL-mediated inhibition of NF-κB activity decreases aggressive growth characteristics of prostate cancer cells in vitro.

Keywords: IL-6; IL-8; MMP-9; NF-κB; ROS; adhesion; apoptosis; cytokines; piperlongumine; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Dioxolanes / pharmacology*
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*

Substances

  • Dioxolanes
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Plant Extracts
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 9
  • piperlonguminine