Open AccessBAX enhances paclitaxel-induced apoptosis through a p53-independent pathway
Author(s) -
Thomas Ströbel,
Linda J. Swanson,
Stanley J. Korsmeyer,
Stephen A. Cannistra
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.24.14094
Subject(s) - paclitaxel , apoptosis , cytotoxicity , doxorubicin , transfection , biology , bcl 2 associated x protein , carboplatin , etoposide , vincristine , microbiology and biotechnology , cancer research , cell culture , chemotherapy , programmed cell death , in vitro , cisplatin , caspase 3 , biochemistry , genetics , cyclophosphamide
To investigate the role of BAX in chemotherapy-induced apoptosis, we transfected the SW626 human ovarian cancer cell line, which lacks functional p53, with a cDNA encoding for murine BAX. Immunoblotting revealed that BAX transfectants expressed a mean of 10-fold increased levels of BAX compared with neo-transfected control clones, with similar levels of BCL-2 and BCL-xL . The cytotoxicity of paclitaxel, vincristine, and doxorubicin was significantly enhanced in BAX transfectants compared with control clones, whereas the cytotoxicity profile of carboplatin, etoposide, and hydroxyurea was unchanged. Increased paclitaxel-induced cytotoxicity of BAX clones was associated with enhanced apoptosis, as assessed by morphologic and flow cytometric criteria. These data suggest that sufficient levels of BAX may bypass the need for upstream molecules such as p53 in the process of chemotherapy-induced apoptosis.