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EnglishValproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long-term therapy of epilepsy. Recently, VPA was demonstrated to inhibit histone deacetylases (HDACs) class I enzyme at therapeutically relevant concentrations, thereby, mimicking the prototypical histone deacetylase inhibitors, tricostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA). In the present study, we investigated the cellular effects of VPA, TSA and SAHA on four human melanoma cell lines (WM115, WM266, A375, SK-Mel28) with particular reference to the modulation of regulators of apoptosis, including Bcl-2, BclXL, Mcl-1, Apaf-1, BclXs, NOXA, TRAIL-R1, TRAIL-R2, caspase 8, and survivin). Firstly, we found that VPA induced apoptosis in two of the four human melanoma cell lines, while both TSA and SAHA exhibited an antiproliferative and apoptotic effects in all four cell lines, a different expression of Bcl-2 and BclXL/S occurred. On the other hand, SAHA and VPA modulated differently pro- and antiapoptotic factors. In particular, the treatment with VPA enhanced the level of expression of survivin only in VPAresistant cell lines, whereas down-regulation of survivin was induced by VPA and SAHA in VPA-sensitive cells. In the latter, since activation of caspase 8 was documented, a receptor-mediated apoptosis was suggested. Taken together, our results suggest that HDAC inhibitors may represent a promising therapeutic strategy to treat melanoma.
Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors / F. Facchetti, S. Previdi, M. Ballarini, S. Minucci, P. Perego, C. La Porta. - In: APOPTOSIS. - ISSN 1360-8185. - 9:5(2004), pp. 573-582.
| Titolo: | Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors | |
| Autori: | FACCHETTI, FLORIANA (Primo) PEREGO, PAOLA (Penultimo) LAPORTA, CATERINA ANNA MARIA (Ultimo) | |
| Parole Chiave: | BclX/Bcl2; melanoma; SAHA; survivin; TRAIL; valproic acid | |
| Settore Scientifico Disciplinare: | Settore MED/04 - Patologia Generale | |
| Data di pubblicazione: | 2004 | |
| Rivista: | ||
| Tipologia: | Article (author) | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1023/B:APPT.0000038036.31271.50 | |
| Appare nelle tipologie: | 01 - Articolo su periodico |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| apoptosis 2004.pdf | Pre-print (manoscritto inviato all'editore) | Open Access Visualizza/Apri | ||
| apoptosis 2004.pdf | Publisher's version/PDF | Open Access Visualizza/Apri |
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