Reference : Ascorbate potentiates the cytotoxicity of menadione leading to an oxidative stress th...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/32479
Ascorbate potentiates the cytotoxicity of menadione leading to an oxidative stress that kills cancer cells by a non-apoptotic caspase-3 independent form of cell death
English
Verrax, Julien mailto [Université Catholique de Louvain - UCL > Département des Sciences Pharmaceutiques > Unité de pharmacocinétique, métabolisme, nutrition et toxicologie > >]
Cadrobbi, Julie [Université Catholique de Louvain - UCL > Département des Sciences Pharmaceutiques > unité de Pharmacocinétique, métabolisme, nutrition et toxicologie > >]
Marques, Carole [Université Catholique de Louvain - UCL > Département de Pharmacologie > Unité de Pharmacocinétique, métabolosime, nutrition et toxicologie > >]
Taper, Henryk [Université Catholique de Louvain - UCL > Département de Pharmacologie > Unité de Pharmacocinétique, métabolisme, nutrition et toxicologie > >]
Habraken, Yvette mailto [Université de Liège - ULg > > Virologie - Immunologie >]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > Virologie - Immunologie > > >]
Calderon, Pedro Buck mailto [Université Catholique de Louvain - UCL > Département des Sciences Pharmaceutiques > Unité de pharmacocinétique, métabolisme nutrition et toxicologie > >]
Mar-2004
Apoptosis : An International Journal on Programmed Cell Death
Kluwer Academic Publ
9
2
223-233
Yes (verified by ORBi)
International
1360-8185
Dordrecht
Netherland
[en] ascorbate ; menadione ; oxidative stress ; autoschizis ; hepatocarcinoma cells
[en] Hepatocarcinoma cells (TLT) were incubated in the presence of ascorbate and menadione, either alone or in combination. Cell death was only observed when such compounds were added simultaneously, most probably due to hydrogen peroxide (H2O2) generated by ascorbate-driven menadione redox cycling. TLT cells were particularly sensitive to such an oxidative stress due to its poor antioxidant status. DNA strand breaks were induced by this association but this process did not correspond to oligosomal DNA fragmentation (a hallmark of cell death by apoptosis). Neither caspase-3-like DEVDase activity, nor processing of procaspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) were observed in the presence of ascorbate and menadione. Cell death induced by such an association was actively dependent on protein phosphorylation since it was totally prevented by preincubating cells with sodium orthovanadate, a tyrosine phosphatase inhibitor. Finally, while H2O2, when administered as a bolus, strongly enhances a constitutive basal NF-kappaB activity in TLT cells, their incubation in the presence of ascorbate and menadione results in a total abolition of such a constitutive activity.
Researchers
http://hdl.handle.net/2268/32479
10.1023/B:APPT.0000018804.26026.1a

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