Caspase 8/10 are not mediating apoptosis in neuroblastoma cells treated with CDK inhibitory drugs.
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 9-24.], 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.
Ribas
Judit
J
Molecular Pharmacology Laboratory, Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Catalunya, Spain.
Gomez-Arbones
Xavier
X
Boix
Jacint
J
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D007701:Kinetin / Q000494:pharmacology; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D013997:Time Factors
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011687:Purines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000077546:Roscovitine; C090046:olomoucine; D018844:Cyclin-Dependent Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human; D007701:Kinetin