2--4--dihydroxy-6--methoxy-3--5--dimethylchalcone and Carcinoma

Previously we have shown that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated from the buds of Cleistocalyx operculatus, significantly inhibits the growth of human liver cancer SMMC-7721 cells and is able to induce apoptosis of SMMC-7721 cells in vitro. Here we report the antitumor effects of DMC in vivo, using a solid human tumor xenograft mouse model using human liver cancer SMMC-7721 cells. The average tumor weights in the control group and in mice injected with 150 mg/kg DMC were 1.42+/-0.11 g and 0.59+/-0.12 g, respectively. Flow cytometric analysis of the tumor cell population demonstrated an aneuploid peak (representing 33.60+/-0.80% of the total in mice injected with 150 mg/kg DMC). To our knowledge, this is the first time that chalcone compounds have been applied to a human tumor xenograft model.

Topics: Animals; Carcinoma; Chalcone; Chalcones; Disease Models, Animal; Drug Screening Assays, Antitumor; Liver Neoplasms; Mice; Myrtaceae; Plant Extracts; Transplantation, Heterologous

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 microM DMC was present simultaneously with doxorubicin, the IC50 of DOX on KB-A1 cells decreased from 13.9 +/- 0.7 microg/ml to 3.6 +/- 0.7 microg/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 microg/ml doxorubicin combined with 5, 10, 20 microM 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.

Topics: Animals; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma; Chalcone; Chalcones; Doxorubicin; Drug Resistance, Multiple; Gene Expression Profiling; Humans; Mice; Mice, Nude; Mouth Neoplasms; Myrtaceae; Polymerase Chain Reaction; Transplantation, Heterologous; Tumor Cells, Cultured