BAX enhances paclitaxel-induced apoptosis through a p53-independent pathway.
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.
Strobel
T
T
Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Swanson
L
L
Korsmeyer
S
S
Cannistra
S A
SA
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000633:toxicity; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000633:toxicity; D015151:Immunoblotting; D007700:Kinetics; D051379:Mice; D010051:Ovarian Neoplasms; D017239:Paclitaxel / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014750:Vincristine / Q000633:toxicity; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D014750:Vincristine; D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D006918:Hydroxyurea