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Article

Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells

  • Authors:
    • Xin Wang
    • Chen Tan
    • Guo Wang
    • Jing-Jing Cai
    • Li-Ping Wang
    • Julianne Imperato-McGinley
    • Yuan-Shan Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Medicine/Endocrinology, Weill Cornell Medicine, New York, NY 10065, USA
  • Pages: 1601-1610
    |
    Published online on: September 27, 2017
       https://doi.org/10.3892/ijo.2017.4138
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Abstract

Chemotherapy is a vital therapeutic strategy for castration-resistant prostate cancer (CRPC). We have previously shown that NSC606985 (NSC), a camptothecin (CPT) analog, induced cell apoptosis via interacting with topoisomerase I (Topo I) in prostate cancer cells. In the present study, the effect and mechanism of CPT analogs in LAPC4 cells were investigated. LAPC-4 cells were treated with NSC, CPT, and topotecan. Cell proliferation, apoptosis, and protein kinase Cδ (PKCδ) subcellular activation were measured at different doses and time-points, with or without PKCδ inhibition or knockdown of PKCδ expression. NSC at doses ranging from 10 to 100 nM induced a dose-dependent increase in viable cell number and DNA biosynthesis with mild cell apoptosis, whereas, at doses ranging from 500 nM to 5 mM, NSC produced a dose-dependent decrease in cell proliferation and DNA biosynthesis with a significant induction of cell apoptosis. Both NSC-induced cell proliferation and apoptosis were blocked by knockdown of PKCδ with a specific RNAi, or by the co-administration of rottlerin, a PKCδ inhibitor. Moreover, NSC produced a dose-dependent subcellular activation of PKCδ. The dose-dependent dual action of NSC is mediated at least in part through the differential subcellular activation of PKCδ in LAPC4 cells. The demonstration of a differential cell response to camptothecin analogs would facilitate the identification of biomarker(s) to CPT sensitivity and promote the personalization of CPT chemotherapy in CRPC.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Tan C, Wang G, Cai J, Wang L, Imperato-McGinley J and Zhu Y: Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells. Int J Oncol 51: 1601-1610, 2017.
APA
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., & Zhu, Y. (2017). Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells. International Journal of Oncology, 51, 1601-1610. https://doi.org/10.3892/ijo.2017.4138
MLA
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., Zhu, Y."Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells". International Journal of Oncology 51.5 (2017): 1601-1610.
Chicago
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., Zhu, Y."Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells". International Journal of Oncology 51, no. 5 (2017): 1601-1610. https://doi.org/10.3892/ijo.2017.4138
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Tan C, Wang G, Cai J, Wang L, Imperato-McGinley J and Zhu Y: Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells. Int J Oncol 51: 1601-1610, 2017.
APA
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., & Zhu, Y. (2017). Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells. International Journal of Oncology, 51, 1601-1610. https://doi.org/10.3892/ijo.2017.4138
MLA
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., Zhu, Y."Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells". International Journal of Oncology 51.5 (2017): 1601-1610.
Chicago
Wang, X., Tan, C., Wang, G., Cai, J., Wang, L., Imperato-McGinley, J., Zhu, Y."Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells". International Journal of Oncology 51, no. 5 (2017): 1601-1610. https://doi.org/10.3892/ijo.2017.4138
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