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.

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(6), 1293-1303 [10.3892/ijo_32_6_1293].

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

GRAZIANI, GRAZIA;MUZI, ALESSIA;SICA, GIUSEPPE
2008-01-01

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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
Androgen receptor; Differentiation; Hormone-sensitivity; Prostate cancer cells; Valproic acid
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(6), 1293-1303 [10.3892/ijo_32_6_1293].
Iacopino, F; Urbano, R; Graziani, G; Muzi, A; Navarra, P; Sica, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/38507
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