Unbalanced histone deacetylase (HDAC) hyperactivity is a common feature of tumor cells. Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy. It has recently been recognized as a promising anticancer drug. We investigated the effects of VPA on growth and survival of colon cancer cells. VPA caused growth inhibition and programmed cell death that correlated with histone hyperacetylation. VPA modulated the expression of various factors involved in cell cycle control and apoptosis and induced caspase activation. Interestingly, VPA induced downregulation of c-Src and potentiated the cytotoxic effects of the c-Src inhibitor bosutinib, both in vitro and in vivo. The combination of sublethal doses of VPA and bosutinib led to massive apoptosis of colon cancer cells, irrespective of their genetic background. These results suggest that VPA may be employed as a positive modulator of bosutinib antitumor activity in colorectal cancer.

Mologni, L., Cleris, L., Magistroni, V., Piazza, R., Boschelli, F., Formelli, F., et al. (2009). Valproic acid enhances bosutinib cytotoxicity in colon cancer cells. INTERNATIONAL JOURNAL OF CANCER, 124(8), 1990-1996 [10.1002/ijc.24158].

Valproic acid enhances bosutinib cytotoxicity in colon cancer cells

MOLOGNI, LUCA;MAGISTRONI, VERA;PIAZZA, ROCCO GIOVANNI;GAMBACORTI PASSERINI, CARLO
2009-04

Abstract

Unbalanced histone deacetylase (HDAC) hyperactivity is a common feature of tumor cells. Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy. It has recently been recognized as a promising anticancer drug. We investigated the effects of VPA on growth and survival of colon cancer cells. VPA caused growth inhibition and programmed cell death that correlated with histone hyperacetylation. VPA modulated the expression of various factors involved in cell cycle control and apoptosis and induced caspase activation. Interestingly, VPA induced downregulation of c-Src and potentiated the cytotoxic effects of the c-Src inhibitor bosutinib, both in vitro and in vivo. The combination of sublethal doses of VPA and bosutinib led to massive apoptosis of colon cancer cells, irrespective of their genetic background. These results suggest that VPA may be employed as a positive modulator of bosutinib antitumor activity in colorectal cancer.
Articolo in rivista - Articolo scientifico
Scientifica
HDAC; bosutinib; colon cancer; synergy; c-Src
English
Mologni, L., Cleris, L., Magistroni, V., Piazza, R., Boschelli, F., Formelli, F., et al. (2009). Valproic acid enhances bosutinib cytotoxicity in colon cancer cells. INTERNATIONAL JOURNAL OF CANCER, 124(8), 1990-1996 [10.1002/ijc.24158].
Mologni, L; Cleris, L; Magistroni, V; Piazza, R; Boschelli, F; Formelli, F; GAMBACORTI PASSERINI, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/28637
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