Chinese traditional herbs, such as rhubarb, have been demonstrated anti-cancer function. Rhein ，4, 5- dihydroxyanthraquinone-2-carboxylic acid，is an anthraquinone compound that is enriched in rhubarb with anti-liver cancer, anti-glioma and anti-myeloma activities in vitro and in vivo assays. Breast cancer
occupies the first position among female cancer deaths in Taiwan. The patients whose breast cancer cells over-express the HER2 protein are likely resistant to a variety of chemotherapy agents. In this study, 26 Chinese traditional herb compounds were selected to test the activities and mechanism of anti-breast cancer in vitro assays of MCF-7/WT cells expressing the low level of HER2 and MCF-7/HER2 cells expressing the high level of HER2. MTT assay indicated that rhein showed the best ability to inhibit the growth of both MCF-7/WT cells and MCF-7/HER2 cells among these Chinese traditional herb compounds. The 50%
inhibitory concentration (IC50) value of rhein in MCF-7/WT cells was 83.66 μg/ml, whereas the IC50 value of rhein in MCF-7/ HER2 cells was 47.67 μg/ml. Flow cytometry showed that rhein induces dose-dependent apoptosis. Furthermore, Western blotting demonstrated caspase 3 and caspase 9 dependent apoptosis induced by rhein. Flow cytometry assays showed that rhein significantly increased in the production of reactive oxygen species (ROS) and decreased in the mitochondrial membrane potential (MMP) using.
Moreover, in vivo signaling pathway assay revealed that NF-κB and p53, but not AP1 were activated in rhein-treated MCF-7/WT cells and MCF-7/HER2 cells, being associated with ROS-mediated apoptosis.
Therefore, rhein could be useful for the clinical application of treatment for patients with breast cancer with low and high levels of HER2 expression.
