Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells

  • Authors:
    • Fortunata Iacopino
    • Raffaella Urbano
    • Grazia Graziani
    • Alessia Muzi
    • Pierluigi Navarra
    • Gigliola Sica
  • View Affiliations

  • Published online on: June 1, 2008     https://doi.org/10.3892/ijo.32.6.1293
  • Pages: 1293-1303
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Abstract

Histone deacetylase (HDAC) inhibitors are currently undergoing clinical trials in cancer patients on the basis of their effect on proliferation, differentiation and apoptosis demonstrated in vitro. The goal of this study was to assess the effects of an HDAC inhibitor, valproic acid (VA), on proliferation, androgen-sensitivity, androgen receptor levels and E-cadherin (E-cad) expression in human prostate cancer cells. The effects of VA were evaluated in androgen-sensitive, LNCaP and -insensitive PC-3 human prostate cancer cell lines. Proliferation was assayed by cell counts and protein expression by Western blot analysis. Morphological changes were analysed under an inverted phase contrast microscope. High VA concentrations (1-25 mM) induced a very strong reduction in cell numbers (≈90% with respect to control) of the two cell lines due to drug cytotoxicity. A low concentration (0.45 mM VA) slightly reduced (14%) LNCaP cell proliferation and abolished the response to androgen. In the PC-3 cells, the same concentration of VA had a more pronounced (40%) inhibitory effect and induced a response to dihydrotestosterone in terms of an enhancement in cell growth. These events were associated with morphological changes, an absence of cytotoxicity, an increase in androgen receptor levels, and, in PC-3 cells, an enhancement in E-cad expression which may be ascribed to VA differentiative action. Our findings, obtained with a VA dose (0.45 mM), which is consistent with plasma concentrations reached under oral administration of therapeutical doses in patients treated for different diseases, suggest that VA might have clinical value in prostate cancer therapy in androgen-sensitive and -insensitive tumors.

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June 2008
Volume 32 Issue 6

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

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Spandidos Publications style
Iacopino F, Urbano R, Graziani G, Muzi A, Navarra P and Sica G: Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells. Int J Oncol 32: 1293-1303, 2008
APA
Iacopino, F., Urbano, R., Graziani, G., Muzi, A., Navarra, P., & Sica, G. (2008). Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells. International Journal of Oncology, 32, 1293-1303. https://doi.org/10.3892/ijo.32.6.1293
MLA
Iacopino, F., Urbano, R., Graziani, G., Muzi, A., Navarra, P., Sica, G."Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells". International Journal of Oncology 32.6 (2008): 1293-1303.
Chicago
Iacopino, F., Urbano, R., Graziani, G., Muzi, A., Navarra, P., Sica, G."Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells". International Journal of Oncology 32, no. 6 (2008): 1293-1303. https://doi.org/10.3892/ijo.32.6.1293