(R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastorna cells to nutlin-3-induced apoptosis

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2006
Author
Ribas i Fortuny, Judit
Boix Torras, Jacint
Meijer, Laurent
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Ribas i Fortuny, Judit; Boix Torras, Jacint; Meijer, Laurent; . (2006) . (R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastorna cells to nutlin-3-induced apoptosis. Experimental Cell Research, 2006, vol. 312, num. 12, p. 2394-2400. https://doi.org/10.1016/j.yexcr.2006.04.021.
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Abstract
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.
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http://hdl.handle.net/10459.1/48093
DOI
https://doi.org/10.1016/j.yexcr.2006.04.021
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Experimental Cell Research, 2006, vol. 312, num. 12, p. 2394-2400
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