title: Co-transduction of Apaf-1 and caspase-9 augments etoposide-induced apoptosis in U-373MG glioma cells.
abstract: Several apoptosis-related genes have been reported to be involved in chemotherapy-induced apoptosis in cancers. An assessment of the relationship between expression of those genes and the degree of chemotherapy-induced apoptosis may be useful in improving the efficacy of cancer therapy. We transduced Apaf-1 (apoptotic protease-activating factor-1) and caspase-9 into U-373MG glioma cells using adenovirus (Adv) vectors in the presence of etoposide and evaluated the degree of apoptosis. The degree of apoptosis in etoposide-treated U-373MG cells infected with Adv for Apaf-1 (Adv-APAF1) was higher (27%) than that in cells infected with control Adv (14%), that in cells infected with Adv for caspase-9 (Adv-Casp9) was higher (34%) than that in cells infected with Adv-APAF1, and that in cells infected with both Adv-APAF1 and Adv-Casp9 was the highest (41%). Treatment with etoposide increased expression of p53 and decreased expression of Bcl-X(L) in U-373MG cells which harbored mutant p53. These results indicate that the expression of Apaf-1 and caspase-9 may be important determinants in predicting the sensitivity of cancers to chemotherapy. Adv-mediated co-transduction of Apaf-1 and caspase-9 should render cancer cells highly sensitive to chemotherapy.
authors.affiliation: Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan. shinoura-k@komagome-hospital.bunkyo.tokyo.jp
authors.forename: N
authors.initials: N
authors.lastname: Shinoura
authors.forename: S
authors.initials: S
authors.lastname: Sakurai
authors.forename: A
authors.initials: A
authors.lastname: Asai
authors.forename: T
authors.initials: T
authors.lastname: Kirino
authors.forename: H
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005047:Etoposide / Q000494:pharmacology*; D016158:Genes, p53; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein
chemical_list: C506592:APAF1 protein, human; D000972:Antineoplastic Agents, Phytogenic; D053477:Apoptotic Protease-Activating Factor 1; C494811:BCL2L1 protein, human; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D005047:Etoposide; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases