Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. Mulberry fruit is rich in phenolic compounds and flavonoids and exhibits chemopreventive activities. In this study, mulberry water extract (MWE) was used as a supplement to synergize with the effects of paclitaxel in the treatment of the TSGH 8301 human bladder cancer cell line.
Treatment with paclitaxel combined with MWE (paclitaxel/MWE) enhanced the cytotoxicity of paclitaxel and induced severe G2/M arrest, mitotic catastrophe and subsequent apoptosis, as shown by MTT assay, HE staining and flow cytometry analyses. Differences in the expression and activation of Aurora A and Plk1between cells treated with paclitaxel/MWE and paclitaxel alone suggested that the combined treatment caused a defect in the early steps of cytokinesis. Paclitaxel/MWE decreased EEA1immunofluorescence staining and increased the expression of PTEN, indicating that the regimen inhibited the formation of the recycling endosome, which is required for cytokinesis. Paclitaxel/MWE also retarded tumor growth in a TSGH 8301 xenograft model via activation of PTEN and Caspase 3. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel through MWE supplementation by promoting mitotic catastrophe through the activation of PTEN, providing a novel and effective therapeutic option for bladder cancer treatment strategies.
Scientific reports. 2016 Feb 03*** epublish ***
Nien-Cheng Chen, Charng-Cherng Chyau, Yi-Ju Lee, Hsien-Chun Tseng, Fen-Pi Chou
Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan., Research Institute of Biotechnology, Hung Kuang University, Taichung City, Taiwan., Department of Pathology, Chung Shan Medical University Hospital, Taichung City, Taiwan., Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City, Taiwan., Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.