title: Protein delivery of caspase-3 induces cell death in malignant C6 glioma, primary astrocytes and immortalized and primary brain capillary endothelial cells.
abstract: Most brain tumors consist of transformed glia cells and are highly vascularized by capillary endothelial cells. The aim of the present study therefore was to deliver pro-apoptotic caspase-3 into malignant C6 glioma and immortalized rBCEC4 brain endothelial cells to induce cell death. Both cell lines were transfected with a reporter protein (beta-galactosidase) using lipid-mediated gene transfer (FuGENE6) or using the novel protein delivery reagent BioPORTER. beta-Galactosidase protein was successfully delivered into both cells, the protein expression peaked around day 2 and was transient. Delivery of caspase-3 induced TUNEL-positive cell death of both cell types. As a control, caspase-3 was also delivered to non-neoplastic primary astrocytes and endothelial cells and induced cell death. In conclusion BioPORTER-protein delivery of pro-apoptotic molecules may provide a potent tool to cause death of the cells in brain tumors, however, this method is limited due to its toxicity to non-malignant cells.
authors.affiliation: Laboratory of Psychiatry, University Clinic of Psychiatry, Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zassler
authors.forename: Ingolf E
authors.initials: IE
authors.lastname: Blasig
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000187:drug effects* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics* / Q000494:pharmacology*; D016923:Cell Death; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D018014:Gene Transfer Techniques; D005910:Glioma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051381:Rats; D013194:Staining and Labeling
chemical_list: C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases