The semisynthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-κB.
Br J Cancer
; 104(3): 437-40, 2011 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-21245867
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-(ß-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-κB (NF-κB) 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-κB activation. CONCLUSION: These results suggest that reduction of doxorubicin-induced NF-κB activation by monoHER, which sensitises cancer cells to apoptosis, is involved in the chemosensitising effect of monoHER in human liposarcoma cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sarcoma
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Flavonoides
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FN-kappa B
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Apoptosis
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Hidroxietilrutósido
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Liposarcoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido