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.
Jpn J Cancer Res
; 91(12): 1264-8, 2000 Dec.
Article
in En
| MEDLINE
| ID: mdl-11123425
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins
/
Apoptosis
/
Proto-Oncogene Proteins c-bcl-2
/
Cytochrome c Group
/
Mitochondria
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Jpn J Cancer Res
Journal subject:
NEOPLASIAS
Year:
2000
Document type:
Article
Affiliation country:
Japan