title: Parthenolide complements the cell death-inducing activity of doxorubicin in melanoma cells.
abstract: BACKGROUND
  Melanoma is characterized by high resistance to chemotherapy. The aim of this study was to investigate combined effects of doxorubicin and parthenolide on melanoma cells.
  
  
  METHODS
  Thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry were used to evaluate viability. The p53 levels and Poly-ADP ribose polymerase (PARP) cleavage were assessed by western blot. Electrophoretic mobility shift assay (EMSA) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate changes in nuclear factor-κB (NF-κB) activity and gene expression, respectively.
  
  
  RESULTS
  Both drugs reduced the viability of melanoma cells and induced apoptosis. Expression of the ATP-binding cassette sub-family B member-5 (ABCB5) transporter was enhanced by doxorubicin. Doxorubicin induced activity of p53 and NF-κB. Parthenolide markedly reduced the constitutive and doxorubicin-induced NF-κB activity measured as the nuclear NF-κB, and expression of matrix metalloproteinase-9 (MMP9) and it had no effect on p53.
  
  
  CONCLUSIONS
  Doxorubicin and parthenolide affected distinct pathways in melanoma, and parthenolide was capable of combating some pro-survival effects of doxorubicin in the combined treatment. This provides a rationale for in vivo investigation of this drug combination.
authors.affiliation: Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street; 92-215 Lodz, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
authors.forename: Agata
authors.initials: A
authors.lastname: Szulawska-Mroczek
authors.forename: Mariusz L
authors.initials: ML
authors.lastname: Hartman
authors.forename: Dariusz
authors.initials: D
authors.lastname: Nejc
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czyz
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; C002669:parthenolide; D004317:Doxorubicin
keywords: ABCB5; NF-κB; doxorubicin; melanoma; p53; parthenolide