Multidrug resistance reversal effect of DMC derived from buds of Cleistocalyx operculatus in human hepatocellular tumor xenograft model

BACKGROUND: 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. RESULTS: 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. CONCLUSION: All results suggested that DMC reverses 5‐FU resistance, with a benign side effects profile. Copyright © 2011 Society of Chemical Industry