Bax induction activates apoptotic cascade via mitochondrial cytochrome c release and Bax overexpression enhances apoptosis induced by chemotherapeutic agents in DLD-1 colon cancer cells.
Cancer cells express different levels of apoptosis-promoting Bax protein. The present study evaluated whether induction of Bax initiates apoptosis and whether Bax overexpression enhances apoptosis induced by several chemotherapeutic agents in DLD-1 colon cancer cells, which originally express a high level of endogenous Bax protein and a low level of Bcl-2 protein. To investigate these two points, parental DLD-1 cells were transfected with the Tet-On Bax induction system (pTet-On and pTRE-Bax plasmids), and stable transduced cells were obtained. Induction of Bax by the Tet-On system initiated cytochrome c release from mitochondria, caspase-3 activation, and apoptosis to some extent in DLD-1 cells. Apoptosis induced by a chemotherapeutic agent, 5-fluorouracil, mitomycin C, paclitaxel, doxorubicin, or cisplatin, was enhanced by Bax overexpression. These findings suggest that Bax-overexpression-based gene therapy combined with chemotherapy would be effective in the treatment of colon cancer.
Kobayashi
T
T
The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, 514-8507, Japan. tohruk@clin.medic.mie-u.ac.jp
Sawa
H
H
Morikawa
J
J
Zhang
W
W
Shiku
H
H
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity; D003110:Colonic Neoplasms; D003574:Cytochrome c Group / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D016685:Mitomycin / Q000633:toxicity; D017239:Paclitaxel / Q000633:toxicity; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D003574:Cytochrome c Group; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D016685:Mitomycin; D004317:Doxorubicin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil