کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2580806 1561638 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cytotoxicity of quinone drugs on highly proliferative human leukemia T cells: Reactive oxygen species generation and inactive shortened SOD1 isoform implications
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Cytotoxicity of quinone drugs on highly proliferative human leukemia T cells: Reactive oxygen species generation and inactive shortened SOD1 isoform implications
چکیده انگلیسی

Drugs containing the quinone group were tested on hyperproliferative leukemia T cells (HLTC: Jhp and Jws) and parental Jurkat cells. Doxorubicin, menadione and adaphostin produced different effects on these cell lines. Rapid doxorubicin-induced cell death in Jurkat cells was mediated by caspase activation. Doxorubicin-induced cell death of HLTCs was delayed due to the absence of caspase-3 and -8 expression. Delayed HLTC cell death was mediated and triggered by the generation of reactive oxygen species (ROS). Other drugs containing quinone groups, such as menadione and adaphostin, were also tested on HLTC and both were toxic by a caspase-independent mechanism. The toxicity of these drugs correlated with the generation of the superoxide anion, which increased and was more effective in HLTCs than in parental Jurkat cells. Accordingly, SOD1 activity was much lower in HLTCs than in Jurkat cells. This lower SOD1 activity in HLTCs was associated not only with the absence of the wild-type (16 kDa) SOD1 monomer but also with the presence of a shortened (14 kDa) SOD1 monomer isoform. Moreover, the cytotoxicity of drugs containing the quinone group was prevented by incubation with manganese(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a cell-permeable superoxide dismutase mimetic and a potent inhibitor of oxidation. These findings could explain the sensitivity of HLTCs to drugs containing the quinone group using a mechanism dependent on oxidative stress. These observations can also be useful to target hyperproliferative leukemias that are resistant to the classical caspase-dependent apoptotic pathway.


► Cytotoxicity of quinone drugs on hyperproliferative leukemia T cells is assessed.
► The mechanism of quinone drugs is mediated by Reactive Oxygen Species generation.
► Increased generation of ROS is associated to and inactive shortened SOD1 isoform.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 198, Issues 1–3, 25 June 2012, Pages 18–28
نویسندگان
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