Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation

  • Authors:
    • José M.. Arencibia
    • Mónica Del Rio
    • Ana Bonnin
    • Rita Lopes
    • Nicholas R. Lemoine
    • Mónica López-Barahona
  • View Affiliations

  • Published online on: December 1, 2005     https://doi.org/10.3892/ijo.27.6.1617
  • Pages: 1617-1623
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Abstract

Doxazosin is a quinazoline-based compound acting as an α-1-adrenergic inhibitor shown to induce apoptosis in prostate cancer cell lines via an α-1-adrenergic receptor-independent mechanism. To better understand the mechanism of doxazosin-induced apoptosis in prostate cancer, we performed cDNA microarray to analyze gene expression changes produced by doxazosin in the androgen-dependent human prostate cancer cell line, LNCaP. We found that 70 and 92 genes were deregulated after 8 and 24 h of doxazosin treatment, respectively. These genes are involved in several cellular processes such as cell-cycle regulation, cell adhesion and signal transduction pathways. Strikingly, we found that doxazosin induces deregulation of genes implicated in DNA replication and repair, such as GADD45A, XRCC5 and PRKDC. These facts, together with the demonstration of the ability of doxazosin to bind DNA, allowed us to propose a novel mechanism of action for doxazosin in prostate cancer cells that implies DNA-damage mediated apoptosis by down-regulation of XRCC5 and PRKDC genes.

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December 2005
Volume 27 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Arencibia, J.M., Del Rio, M., Bonnin, A., Lopes, R., Lemoine, N.R., & López-Barahona, M. (2005). Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation. International Journal of Oncology, 27, 1617-1623. https://doi.org/10.3892/ijo.27.6.1617
MLA
Arencibia, J. M., Del Rio, M., Bonnin, A., Lopes, R., Lemoine, N. R., López-Barahona, M."Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation". International Journal of Oncology 27.6 (2005): 1617-1623.
Chicago
Arencibia, J. M., Del Rio, M., Bonnin, A., Lopes, R., Lemoine, N. R., López-Barahona, M."Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation". International Journal of Oncology 27, no. 6 (2005): 1617-1623. https://doi.org/10.3892/ijo.27.6.1617