Caspase 8/10 are not mediating apoptosis in neuroblastoma cells treated with CDK inhibitory drugs

Abstract

Olomoucine and Roscovitine are pharmacological inhibitors of cyclin-dependent kinases (CDK) displaying a promising profile as anticancer agents. Both compounds are effective inductors of apoptosis in a human neuroblastoma cell line, SH-SY5Y. The characterization of this process had suggested the involvement of an extrinsic pathway [Ribas, J., Boix, J., 2004. Cell differentiation, Caspase inhibition, and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs. Exp. Cell Res. 295 9<br>24.], which depends on either Caspase 8 or Caspase 10 activation. However, neither Caspase 8 nor Caspase 10 is expressed in SH- SY5Y cells because of gene silencing. Upon Olomoucine or Roscovitine treatment, no re-expression of Caspase 8 or Caspase 10 was found. Therefore, in SH-SY5Y cells, this type of drugs is not triggering a canonical, Caspase 8/10-mediated, extrinsic apoptotic pathway. © 2005 Elsevier B.V. All rights reserved.