Valproic acid is a well-known antiepileptic drug that was recently discovered to have a wide-spectrum antitumoral action in several tumors. In our work, we tested the proapoptotic activity of valproic acid in prostate cancer. Valproic acid-induced apoptosis was described by several in-vitro assays in three prostate cancer cell lines: two representing the prototype of advanced, clinically untreatable stages of prostate progression, PC3 and DU145, and one resembling a more differentiated androgen-sensitive tumor, LNCaP. We observed that valproic acid was a potent and early apoptotic inducer, mainly in less-differentiated prostate cancer cell lines. The molecular analysis of the apoptotic machinery involved in valproic acid action revealed a central role in Bcl-2 downmodulation. When prostate cancer cells were treated for a longer time with valproic acid, we detected an enhancement of Fas-dependent apoptosis associated with an overexpression in Fas and Fas ligand. Our data indicate that the use of valproic acid may be a suitable therapeutic agent in the control of prostate cancer progression and its action appears particularly relevant in the control of refractory stages of prostate cancer. Anti-Cancer Drugs 17:1141-1150 (c) 2006 Lippincott Williams & Wilkins.

Angelucci, A., Valentini, A., Millimaggi, D., Gravina, G., Miano, R., Dolo, V., et al. (2006). Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. ANTI-CANCER DRUGS, 17(10), 1141-1150 [10.1097/01.cad.0000236302.89843.fc].

Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways

MIANO, ROBERTO;FEDERICI, GIORGIO;BERNARDINI, SERGIO
2006-01-01

Abstract

Valproic acid is a well-known antiepileptic drug that was recently discovered to have a wide-spectrum antitumoral action in several tumors. In our work, we tested the proapoptotic activity of valproic acid in prostate cancer. Valproic acid-induced apoptosis was described by several in-vitro assays in three prostate cancer cell lines: two representing the prototype of advanced, clinically untreatable stages of prostate progression, PC3 and DU145, and one resembling a more differentiated androgen-sensitive tumor, LNCaP. We observed that valproic acid was a potent and early apoptotic inducer, mainly in less-differentiated prostate cancer cell lines. The molecular analysis of the apoptotic machinery involved in valproic acid action revealed a central role in Bcl-2 downmodulation. When prostate cancer cells were treated for a longer time with valproic acid, we detected an enhancement of Fas-dependent apoptosis associated with an overexpression in Fas and Fas ligand. Our data indicate that the use of valproic acid may be a suitable therapeutic agent in the control of prostate cancer progression and its action appears particularly relevant in the control of refractory stages of prostate cancer. Anti-Cancer Drugs 17:1141-1150 (c) 2006 Lippincott Williams & Wilkins.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/24 - Urologia
English
Con Impact Factor ISI
Bcl-2; Fas; FasL; histone deacetylase; mitochondrial depolarization
PMID: 17075313
Angelucci, A., Valentini, A., Millimaggi, D., Gravina, G., Miano, R., Dolo, V., et al. (2006). Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. ANTI-CANCER DRUGS, 17(10), 1141-1150 [10.1097/01.cad.0000236302.89843.fc].
Angelucci, A; Valentini, A; Millimaggi, D; Gravina, G; Miano, R; Dolo, V; Vicentini, C; Bologna, M; Federici, G; Bernardini, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/40489
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