Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species?
| العنوان: | Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species? |
|---|---|
| المؤلفون: | Groninger, E, Meeuwsen-De Boer, GJ, Kamps, WA, De Bont, ESJM |
| المساهمون: | Faculteit Medische Wetenschappen/UMCG, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL) |
| المصدر: | International journal of oncology, 21(6), 1339-1345. SPANDIDOS PUBL LTD |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | reactive oxygen species, EXPRESSION, CYTOCHROME-C RELEASE, COMPLEX, apoptosis, BCL-2, microtubule disrupting drugs, IN-VITRO, PROTEIN-KINASE, vincristine, mitochondria, ACTIVATION, Jurkat cells, DEATH RECEPTORS, PHOSPHORYLATION, LEUKEMIA |
| الوصف: | Vincristine (VCR), a microtubule interfering anticancer agent, plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL). The route of VCR induced apoptosis in ALL cells is not well defined. In this study we demonstrated caspase-9 and -3 activation in vivo in bone marrow leukaemic cells of a child with newly diagnosed ALL, after treatment with a single dose of VCR. We hypothesized that VCR induced apoptosis in ALL cells proceeds by a mitochondrial controlled pathway. We further studied the route of VCR induced apoptosis in Jurkat acute lymphoblastic leukaemia cells. First we showed that VCR induces activation of caspase-9 and -3 in Jurkat cells. With the caspase-9 inhibitor Z-LEHD-FMK we proved that caspase-9 was activated prior to caspase-3. Loss of mitochondrial transmembrane potential was independent of caspase-9 activation. To confirm the mitochondrial role in VCR induced apoptosis, the effect of blocking the mitochondrial route upstream of caspase-9 activation was investigated at two different levels: reactive oxygen species (ROS) scavenging and Bcl-2 overexpression. Generation of ROS was detected early in Jurkat cells during VCR exposure. Ascorbic acid, a ROS scavenger, inhibited ROS generation as well as caspase-9 and -3 activation and cell death induced by VCR. Furthermore, in Bcl-2 overexpressing Jurkat cells mitochondrial membrane potential changes, caspase-9 and -3 activation and cell death upon VCR exposure were decreased, in comparison to parental Jurkat cells. However, generation of ROS was not decreased in Jurkat cells with Bcl-2 overexpression. We concluded that ROS play a regulatory role in the initial phase of a mitochondrial controlled pathway of VCR induced apoptosis in Jurkat cells. |
| اللغة: | English |
| تدمد: | 1019-6439 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=narcis______::0dfd731b0d124ecb9fac0dacaac4c2cb https://research.rug.nl/en/publications/bada1500-bf91-4667-be53-d0d27eba9427 |
| Rights: | RESTRICTED |
| رقم الانضمام: | edsair.narcis........0dfd731b0d124ecb9fac0dacaac4c2cb |
| قاعدة البيانات: | OpenAIRE |
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