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(R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastorna cells to nutlin-3-induced apoptosis
Ribas i Fortuny, Judit; Boix Torras, Jacint; Meijer, Laurent
In this study, we have analyzed the consequences, on several neuroblastoma cell lines, of combined treatments with (R)-roscovitine (CYC202, Seliciclib), a CDK inhibitory drug, and nutlin-3, a p53 activating drug. Both compounds were found to synergize, causing significant levels of apoptosis in cultured cells when combined at sublethal concentrations. In SH-SY5Y cells, Bcl-XL protein overexpression protected from apoptosis induced by either nutlin-3 alone or the (R)-roscovitine plus nutlin-3 association but failed to prevent apoptosis triggered by (R)-roscovitine alone. Moreover, Western blot studies showed that (R)-roscovitine increased nutlin-3-mediated p53 stabilization. Therefore, we conclude the contribution of (R)-roscovitine to the synergism is basically the sensitization of SH-SY5Y cells to the action of nutlin-3 on p53. The relevance of this pharmacological synergism with respect to the treatment of neuroblastoma is discussed.
2006
Apoptosis
Cell Cycle
Nutlins
p53
Roscovitine
Apoptosi
Càncer
Cicle cel·lular
Apoptosis
Cancer
Cell cycle
(c) Elsevier, 2006
Article
Elsevier
         

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