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Sci Rep. 2016 Feb 3;6:20417. doi: 10.1038/srep20417.

Promotion of mitotic catastrophe via activation of PTEN by paclitaxel with supplement of mulberry water extract in bladder cancer cells.

Author information

1
Institute of Biochemistry, Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
2
Research Institute of Biotechnology, Hung Kuang University, Taichung City, Taiwan.
3
Department of Pathology, Chung Shan Medical University Hospital, Taichung City, Taiwan.
4
Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City, Taiwan.
5
College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
6
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City, Taiwan.

Abstract

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 Plk1 between 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 EEA1 immunofluorescence 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.

PMID:
26838546
PMCID:
PMC4738303
DOI:
10.1038/srep20417
[Indexed for MEDLINE]
Free PMC Article

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