2--4--dihydroxy-6--methoxy-3--5--dimethylchalcone and Disease-Models--Animal

Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its reversal effects on cancer cell MDR.. A human hepatocellular tumor xenograft model was established with the BEL-7402/5-FU cell line. Combined 5-fluorouracil (5-FU) and DMC (40 mg kg(-1) ) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor tissues and increase caspase-3 activity. Also, combined therapy resulted in enhanced tumor apoptotic and reduced proliferative activities relative to 5-FU alone. Examining body weight and other signs of unwanted toxicity of the different treatment groups revealed no significant signs of adverse effects.. All results suggested that DMC reverses 5-FU resistance, with a benign side effects profile.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; Chalcones; Disease Models, Animal; Drug Resistance, Multiple; Female; Fluorouracil; Humans; Liver Neoplasms; Meristem; Mice; Mice, Inbred BALB C; Mice, Nude; Myrtaceae; Phytotherapy; Plant Extracts; Transplantation, Heterologous; Xenograft Model Antitumor Assays

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