Reactive oxygen species-mediated activation of JNK and down-regulation of DAXX are critically involved in penta-O-galloyl-beta-d-glucose-induced apoptosis in chronic myeloid leukemia K562 cells

2012 ◽  
Vol 424 (3) ◽  
pp. 530-537 ◽  
Author(s):  
Tae-Rin Kwon ◽  
Soo-Jin Jeong ◽  
Hyo-Jeong Lee ◽  
Hyo-Jung Lee ◽  
Eun Jung Sohn ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reactive Oxygen ◽  
K562 Cells ◽  
Oxygen Species ◽  
Down Regulation ◽  
Induced Apoptosis

scholarly journals Reactive oxygen species in BCR-ABL1-expressing cells – relevance to chronic myeloid leukemia

2016 ◽  
Vol 64 (1) ◽  
Author(s):  
Joanna Antoszewska-Smith ◽  
Elzbieta Pawlowska ◽  
Janusz Błasiak
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Continuous Production ◽  
Chromosomal Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tki Resistance ◽  
Stem And Progenitor Cells

Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells.  CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis. Introducing imatinib and other tyrosine kinase inhibitors (TKIs) to CML therapy radically improved its outcome, but TKIs-resistance became an emerging problem. TKI-resistance can be associated with even higher ROS production than in TKI-sensitive cells. Therefore, ROS-induced self-mutagenesis of BCR-ABL1 can be crucial for CML progression and TKI resistance and in this way should be taken into account in therapeutic strategies. As a continuous production of ROS by BCR-ABL1 would lead to its self-destruction and death of CML cells, there must be mechanisms controlling this phenomenon. These can be dependent on DNA repair, which is modulated by BCR-ABL1 and can be different in CML stem and progenitor cells. Altogether, the mechanisms of the involvement of BCR-ABL1 in ROS signaling can be involved in CML progression and TKI-resistance and warrant further study.

scholarly journals Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid

2015 ◽  
Vol 291 (4) ◽  
pp. 1933-1947 ◽  
Author(s):  
Andrea Comba ◽  
Luciana L. Almada ◽  
Ezequiel J. Tolosa ◽  
Eriko Iguchi ◽  
David L. Marks ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Arachidonic Acid ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Down Regulation ◽  
Induced Apoptosis

Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.

Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation

2008 ◽  
Vol 19 (10) ◽  
pp. 975-981 ◽  
Author(s):  
Jolie Kiemlian Kwee ◽  
Diogo Gomes Luque ◽  
Ana Carolina dos Santos Ferreira ◽  
Flavia da Cunha Vasconcelos ◽  
Karina Lani Silva ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reactive Oxygen ◽  
Leukemia Cells ◽  
Oxygen Species
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