Explore the Protective Effect and Mechanism of Antioxidant Chinese Medicine on Doxorubicin-Induced Cardiotoxicity

Doxorubicin (DOX) is a highly effective anticancer agent used in the treatment of various solid tumors and malignant hematological disease. However, this drug has proven to cause an accumulative cardiotoxicity that leads to cardiomyopathy and even sudden death due to heart failure. If we can elucidate the mechanisms associated with DOX-induced cardiomyopathy and apply effective therapy, the survival rate of cancer patients would be improved. A variety of approaches aimed at preventing or mitigating the cardiotoxicity of DOX has been tried, but so far, the ability of these treatments seems to have been limited. Previous studies have demonstrated that the major molecular mechanism involved in DOX-induced cardiactocixity is the generation of reactive oxygen species (ROS) and inducing cardiomyocyte apoptosis. Moreover, DOX may trigger the cellular events which result in changing signal pathways. Therefore, it is important to define the molecular mechanisms by which antioxidant drugs inhibit the accumulation of ROS and prevent DOX-induced cardiac injury. Among numerous Chinese herbs, Salvia miltiorrhiza, Crocus sativus, and Rhodiola sachalinensis are considered as strongly antioxidant medicine. Salvia miltiorrhiza, especially, has been proven for its efficacy upon breast cancer therapy. In our proposal, we like to establish both cellular and animal models for evaluation of the toxicity triggered by DOX. Recent developments in functional genomics and proteomics have permitted robust investigations into the molecular mechanisms underlying the cardio-protection exerted by effective components extracted from herbal medicine. Our findings would offer an opportunity for the further applications of Chinese medicine in cancer therapy or side-effects relief in future.

Project ID:PC9807-0306
External Project ID:NSC98-2320-B182-017