Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression

  • Authors:
    • Hideaki Miyake
    • Isao Hara
    • Sadao Kamidono
    • Martin E. Gleave
    • Hiroshi Eto
  • View Affiliations

  • Published online on: March 1, 2003     https://doi.org/10.3892/or.10.2.469
  • Pages: 469-473
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Abstract

We recently reported the powerful antiapoptotic activity of clusterin against various apoptotic stimuli in prostate cancer model systems; however, the precise mode of clusterin action in target cells remains largely unknown. In the present study, we therefore investigated whether intracellular or extracellular action of clusterin plays a crucial role in cytotoxic chemotherapy-induced apoptosis in androgen-independent human prostate cancer PC3 cells, which express a high level of clusterin. The sensitivity of PC3 cells to paclitaxel was increased by pretreatment with monoclonal antibody (mAb) to clusterin or antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene in a dose-dependent manner at up to 50 µg/ml or 1 µM, respectively. However, clusterin mAb failed to further enhance the sensitivity to paclitaxel of PC3 cells simultaneously treated with 1 µM AS clusterin ODN, whereas AS clusterin ODN further induced the apoptosis of cells treated with 50 µg/ml clusterin mAb. Moreover, the effects of clusterin mAb and AS clusterin ODN on PC3 cells were not reversed by additional treatment with exogenous recombinant clusterin protein. These findings suggest that the sensitivity of PC3 cells to paclitaxel-induced cytotoxicity may be regulated by the intracellular rather than extracellular level of clusterin.

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March-April 2003
Volume 10 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Miyake H, Hara I, Kamidono S, Gleave ME and Eto H: Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression. Oncol Rep 10: 469-473, 2003
APA
Miyake, H., Hara, I., Kamidono, S., Gleave, M.E., & Eto, H. (2003). Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression. Oncology Reports, 10, 469-473. https://doi.org/10.3892/or.10.2.469
MLA
Miyake, H., Hara, I., Kamidono, S., Gleave, M. E., Eto, H."Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression". Oncology Reports 10.2 (2003): 469-473.
Chicago
Miyake, H., Hara, I., Kamidono, S., Gleave, M. E., Eto, H."Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression". Oncology Reports 10, no. 2 (2003): 469-473. https://doi.org/10.3892/or.10.2.469