title: Piperlongumine inhibits NF-κB activity and attenuates aggressive growth characteristics of prostate cancer cells.
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.
authors.affiliation: Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Serge
authors.initials: S
authors.lastname: Ginzburg
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Golovine
authors.forename: Petr B
authors.initials: PB
authors.lastname: Makhov
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutikov
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Kolenko
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004148:Dioxolanes / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D018799:Intercellular Adhesion Molecule-1; D015850:Interleukin-6; D016209:Interleukin-8; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D010936:Plant Extracts; C498077:piperlongumine; D010881:Piperidones
keywords: IL-6; IL-8; MMP-9; NF-κB; ROS; adhesion; apoptosis; cytokines; piperlongumine; prostate cancer