The present paper demonstrates that the proteasome inhibitor bortezomib, which behaves as an apoptotic agent in hepatoma HepG2 cells, caused in these cells a decrease in IkappaBalpha level and a consequent increase in NF- kappaB activity. The effect already appeared at 4 h of treatment and preceded the onset of apoptosis which was observed at 24 h. Our results demonstrate that bortezomib-induced IkappaBalpha degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IkappaBalpha level was prevented in a dose-dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8. Bortezomib caused the same effects in non-tumor Chang liver cells, which were not susceptible to the apoptotic effect of the drug. Our results also show that other proteases, such as caspase-3 and calpains, exerted only a limited effect on IkappaBalpha degradation. These findings suggest that caspase-8 can be involved in the control of IkappaBalpha level. In addition, the activation of caspase-8 can exert, at least in the first phase of treatment with bortezomib, a protective effect in both HepG2 and Chang liver cells, favouring the activation of the survival factor NF-kappaB.

CALVARUSO G, GIULIANO M, PORTANOVA P, DE BLASIO A, VENTO R, & TESORIERE G (2006). Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8. MOLECULAR AND CELLULAR BIOCHEMISTRY, 287(1-2)(287), 13-19 [10.1007/s11010-005-9016-3].

Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8.

CALVARUSO, Giuseppe;GIULIANO, Michela;PORTANOVA, Patrizia;DE BLASIO, Anna;VENTO, Renza;TESORIERE, Giovanni
2006

Abstract

The present paper demonstrates that the proteasome inhibitor bortezomib, which behaves as an apoptotic agent in hepatoma HepG2 cells, caused in these cells a decrease in IkappaBalpha level and a consequent increase in NF- kappaB activity. The effect already appeared at 4 h of treatment and preceded the onset of apoptosis which was observed at 24 h. Our results demonstrate that bortezomib-induced IkappaBalpha degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IkappaBalpha level was prevented in a dose-dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8. Bortezomib caused the same effects in non-tumor Chang liver cells, which were not susceptible to the apoptotic effect of the drug. Our results also show that other proteases, such as caspase-3 and calpains, exerted only a limited effect on IkappaBalpha degradation. These findings suggest that caspase-8 can be involved in the control of IkappaBalpha level. In addition, the activation of caspase-8 can exert, at least in the first phase of treatment with bortezomib, a protective effect in both HepG2 and Chang liver cells, favouring the activation of the survival factor NF-kappaB.
CALVARUSO G, GIULIANO M, PORTANOVA P, DE BLASIO A, VENTO R, & TESORIERE G (2006). Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8. MOLECULAR AND CELLULAR BIOCHEMISTRY, 287(1-2)(287), 13-19 [10.1007/s11010-005-9016-3].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/20116
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