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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Dec;91(12):1264–1268. doi: 10.1111/j.1349-7006.2000.tb00913.x

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

Tohru Kobayashi 1,†,✉, Hidehiko Sawa 1,†, Jun Morikawa 1, Wei Zhang 2, Hiroshi Shiku 1
PMCID: PMC5926309  PMID: 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.

Keywords: Bax, Tet‐On system, DLD‐1 colon cancer cells, Mitochondrial cytochrome c release, Chemotherapeutic agents

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