Antitumoral effects of cyclin-dependent kinases inhibitors CR8 and MR4 on chronic myeloid leukemia cell lines

@article{Troadec2015AntitumoralEO,
  title={Antitumoral effects of cyclin-dependent kinases inhibitors CR8 and MR4 on chronic myeloid leukemia cell lines},
  author={Samuel Troadec and M{\'e}lina Blairvacq and Nassima Oumata and Herv{\'e} Galons and Laurent Meijer and Christian Berthou},
  journal={Journal of Biomedical Science},
  year={2015},
  volume={22}
}
BackgroundAlthough Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia, some patients develop resistance with progression of leukemia. Alternative or additional targeting of signalling pathways deregulated in Bcr-Abl-driven chronic myeloid leukemia may provide a feasible option for improving clinical response and overcoming resistance.ResultsIn this study, we investigate ability of CR8 isomers (R-CR8 and S-CR8) and MR4, three derivatives of the cyclin-dependent… 
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References

SHOWING 1-10 OF 61 REFERENCES
CDK Inhibitors Roscovitine and CR8 Trigger Mcl-1 Down-Regulation and Apoptotic Cell Death in Neuroblastoma Cells.
TLDR
Results suggest that the clinical drug roscovitine and its novel analog CR8 induce apoptotic tumor cell death by down-regulating Mcl-1, a key survival factor expressed in all NB cell lines, and may constitute a new approach to treat refractory high-risk NB.
Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma.
TLDR
The data demonstrate that seliciclib has potent cytotoxicity against MM cells that are both sensitive and resistant to conventional therapy as well as primary MM cells from patients, providing the rationale for testing these drug combinations to improve patient outcome in MM.
Inhibition of NF-κB–Mediated Signaling by the Cyclin-Dependent Kinase Inhibitor CR8 Overcomes Prosurvival Stimuli to Induce Apoptosis in Chronic Lymphocytic Leukemia Cells
TLDR
CR8 is a potent CDK inhibitor that subverts pivotal prosurvival and proproliferative signals present in the tumor microenvironment of CLL patient lymphoid organs and supports the clinical development of selective CDK inhibitors as novel therapies for CLL.
Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia.
TLDR
It is reported that endogenous MCL-1's antiapoptotic activity promotes survival during BCR-ABL transformation and in established BCR -ABL(+) leukemia cell lines.
Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression.
TLDR
Nilotinib is a substrate of the multidrug resistance gene product, P-glycoprotein, using verapamil or PSC833 to block binding and mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance.
In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R‐roscovitine)
TLDR
It is shown that CYC202 (R‐roscovitine) is a potent inhibitor of recombinant CDK2/cyclin E kinase activity with an average cytotoxic IC50 of 15.2 μM in a panel of 19 human tumour cell lines, and selectivity for rapidly proliferating cells over non‐proliferating cells is demonstrated.
MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models.
TLDR
Retroviral-mediated transfection of the BCR-ABL(+) AR230 cell line with the MDR1 gene decreased its sensitivity to imatinib, an effect that was also reversed by verapamil, and the possible role of MDR overexpression in clinical resistance to Imatinib remains to be defined.
[Effect of bortezomib on reverse multidrug resistance and XIAP expression in imatinib-resistant primary cells of chronic myeloid leukemia in blastic crisis].
TLDR
The bortezomib may increase the cell apoptosis by inhibition of XIAP expression, so as to provide the experiment evidence to spread bortsomib for the clinical treatment of chronic myeloid leukemia.
Novel agents in CML therapy: tyrosine kinase inhibitors and beyond.
  • J. Melo, C. Chuah
  • Biology, Chemistry
    Hematology. American Society of Hematology. Education Program
  • 2008
TLDR
This review will discuss the current status of the ATP-competitive and non-ATP-competitive Bcr-Abl tyrosine kinase inhibitors, and describe inhibitors acting on targets found in signaling pathways downstream of Bcr -Abl, such as the Ras-Raf-mitogen-activated protein kinase and phosphatidylinositol-3 kinase-Akt-mammalian target of rapamycin pathways.
CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases
TLDR
Results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential and are likely to be effective against non-small-cell lung and nasopharyngeal cancers.
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