The semisynthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-kappaB

H. Jacobs, A. Bast, G.J. Peters, W.J.F. van der Vijgh, G.R.M.M. Haenen

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Background:Despite therapeutic advances, the prognosis of patients with metastatic soft tissue sarcoma (STS) remains extremely poor. The results of a recent clinical phase II study, evaluating the protective effects of the semisynthetic flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) on doxorubicin-induced cardiotoxicity, suggest that monoHER enhances the antitumour activity of doxorubicin in STSs.Methods:To molecularly explain this unexpected finding, we investigated the effect of monoHER on the cytotoxicity of doxorubicin, and the potential involvement of glutathione (GSH) depletion and nuclear factor-kappaB (NF-kappaB) inactivation in the chemosensitising effect of monoHER.Results:MonoHER potentiated the antitumour activity of doxorubicin in the human liposarcoma cell line WLS-160. Moreover, the combination of monoHER with doxorubicin induced more apoptosis in WLS-160 cells compared with doxorubicin alone. MonoHER did not reduce intracellular GSH levels. On the other hand, monoHER pretreatment significantly reduced doxorubicin-induced NF-kappaB activation.Conclusion:These results suggest that reduction of doxorubicin-induced NF-kappaB activation by monoHER, which sensitises cancer cells to apoptosis, is involved in the chemosensitising effect of monoHER in human liposarcoma cells.
Original languageEnglish
Pages (from-to)437-440
Number of pages4
JournalBritish Journal of Cancer
Volume104
Issue number3
DOIs
Publication statusPublished - 1 Feb 2011

Keywords

  • soft tissue sarcoma
  • doxorubicin
  • monoHER
  • glutathione
  • nuclear factor-kappa B
  • apoptosis
  • GLUTATHIONE DEPLETION
  • EUROPEAN-ORGANIZATION
  • CANCER
  • THERAPY
  • ACTIVATION
  • CARDIOTOXICITY
  • CHEMOTHERAPY
  • CURCUMIN
  • TARGET
  • TRIALS

Cite this