Abstract
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus, was investigated for its reversal effects on cancer cell multidrug resistance. DMC potentiated the cytotoxicity of the chemotherapeutic agent doxorubicin to drug-resistant KB-A1 cells. When 5 μM DMC was present simultaneously with doxorubicin, the IC50 of DOX on KB-A1 cells decreased from 13.9 ± 0.7 μg/ml to 3.6 ± 0.7 μg/ml. A human carcinoma xenograft model was established with the KB-A1 cell line. DMC could sensitize the tumors to doxorubicin as indicated by a considerable reduction in tumor weight. DMC increased the intracellular accumulation of doxorubicin in KB-A1 cells. When KB-A1 cells were exposed to 10 μg/ml doxorubicin combined with 5, 10, 20 μM DMC for 4 hours, the intracellular concentrations of doxorubicin were increased 1.4-, 1.8-, 3.1-fold, respectively, in comparison with doxorubicin alone treatment. All results indicated that DMC had reversal effects on the multidrug resistance phenotype.
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