Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-kappaB

Int J Cancer. 2007 Jun 15;120(12):2576-81. doi: 10.1002/ijc.22570.


The transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to be constitutively activated in various human malignancies, including leukemia, lymphoma and a number of solid tumors. NF-kappaB regulates the transcriptional of genes important for tumor invasion, metastasis and chemoresistance. The sesquiterpene lactone parthenolide, an inhibition of NF-kappaB, has been used conventionally to treat migraines and inflammation. In this study, renal cancer cell lines OUR-10 and ACHN were used for in vitro experiments to evaluate growth-inhibitory effects of parthenolide. An OUR-10 xenograft model in nude mice was also used to investigate the in vivo growth-inhibitory effects of parthenolide. Apoptosis in response to treatment of OUR-10 cells with parthenolide was confirmed. Localization of NF-kappaB in response to parthenolide treatment was examined of by immunofluorostaining of OUR-10 cells with antibody against NF-kappaB p65 and by Western blot analysis of OUR-10 cell and tumor nuclear and cytosol fraction. Parthenolide effectively inhibited proliferation of cultured OUR-10 cells and triggered apoptosis in vitro. Subcutaneous injection or oral administration of parthenolide showed significant tumor growth inhibition in the xenograft model via decreased production of interleukin-8 (IL-8) or vascular endothelial growth factor (VEGF). Immunohistochemistry and Western blot analysis showed decreased nuclear localization of NF-kappaB and phosphorylated NF-kappaB protein and subsequently expression of MMP-9, Bcl-xL and Cox-2 in response to parthenolide treatment. These results indicate that parthenolide is a useful in the treatment of renal cell carcinoma and acts via inhibition of NF-kappaB.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / analysis
  • Lactones / pharmacology
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Sesquiterpenes / pharmacology*
  • Time Factors
  • Tumor Burden / drug effects*
  • Vascular Endothelial Growth Factor A / analysis
  • Xenograft Model Antitumor Assays


  • Interleukin-8
  • Lactones
  • NF-kappa B
  • Sesquiterpenes
  • Vascular Endothelial Growth Factor A
  • parthenolide