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 language | English |
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Pages (from-to) | 437-440 |
Number of pages | 4 |
Journal | British Journal of Cancer |
Volume | 104 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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