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Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells

  • Authors:
    • Takeharu Ogura
    • Yoshiyuki Tanaka
    • Hiroki Tamaki
    • Mamoru Harada
  • View Affiliations / Copyright

    Affiliations: Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Japan, Department of Pharmacy, Shimane University Hospital, Shimane, Japan, Department of Immunology, Shimane University Faculty of Medicine, Shimane, Japan
    Copyright: © Ogura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2330-2338
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    Published online on: April 8, 2016
       https://doi.org/10.3892/ijo.2016.3482
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Abstract

Docetaxel is a useful chemotherapeutic agent for the first-line treatment of hormone-refractory prostate cancer. Abnormal expression of Bcl-2 is commonly found in cancer cells, which increases their anti-apoptotic potency and chemoresistance. We investigated the effects of Bcl-2 expression status on the susceptibility of DU145 cells, an androgen-independent human prostate cancer cell line, to docetaxel and other anticancer agents. A panel of Bcl-2-expressing DU145 cell lines was established. Bcl-2 expression levels were unrelated to the susceptibility of DU145 cells to docetaxel. The sensitivity of DU145 cells to cisplatin fluctuated, and the sensitivity to tumor necrosis factor (TNF)-α was decreased by Bcl-2 overexpression. In a xenograft mouse model, overexpression of Bcl-2 drastically decreased the sensitivity of DU145 cells to cisplatin and TNF-α; however, there was no change in the response to docetaxel. Fluorescent microscopy revealed that Bcl-2-overexpression had no effect on the docetaxel-induced death of DU145 cells, but significantly decreased DU145 cell death induced by cisplatin or TNF-α. Interestingly, docetaxel hardly induced caspase-3/7 activation in control or Bcl-2-overexpressing DU145 cells, but did at a low level in LNCaP cells, another prostate cancer cell line. Moreover, in contrast to LNCaP cells, the reduced viabilities of docetaxel-treated control and Bcl-2-overexpressing DU145 cells were not restored by the addition of either a Bid inhibitor or a panel of pro-apoptotic caspase inhibitors. These findings indicate that the antitumor effects of docetaxel on DU145 cells are independent of both Bcl-2 and pro-apoptotic caspases.
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Copy and paste a formatted citation
Spandidos Publications style
Ogura T, Tanaka Y, Tamaki H and Harada M: Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. Int J Oncol 48: 2330-2338, 2016.
APA
Ogura, T., Tanaka, Y., Tamaki, H., & Harada, M. (2016). Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. International Journal of Oncology, 48, 2330-2338. https://doi.org/10.3892/ijo.2016.3482
MLA
Ogura, T., Tanaka, Y., Tamaki, H., Harada, M."Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells". International Journal of Oncology 48.6 (2016): 2330-2338.
Chicago
Ogura, T., Tanaka, Y., Tamaki, H., Harada, M."Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells". International Journal of Oncology 48, no. 6 (2016): 2330-2338. https://doi.org/10.3892/ijo.2016.3482
Copy and paste a formatted citation
x
Spandidos Publications style
Ogura T, Tanaka Y, Tamaki H and Harada M: Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. Int J Oncol 48: 2330-2338, 2016.
APA
Ogura, T., Tanaka, Y., Tamaki, H., & Harada, M. (2016). Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. International Journal of Oncology, 48, 2330-2338. https://doi.org/10.3892/ijo.2016.3482
MLA
Ogura, T., Tanaka, Y., Tamaki, H., Harada, M."Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells". International Journal of Oncology 48.6 (2016): 2330-2338.
Chicago
Ogura, T., Tanaka, Y., Tamaki, H., Harada, M."Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells". International Journal of Oncology 48, no. 6 (2016): 2330-2338. https://doi.org/10.3892/ijo.2016.3482
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