Role of BAX in the Apoptotic Response to Anticancer Agents

To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absenc...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2000-11, Vol.290 (5493), p.989-992
Main Authors: Zhang, Lin, Yu, Jian, Park, Ben Ho, Kinzler, Kenneth W., Vogelstein, Bert
Format: Article
Language:English
Subjects:
Ageing, cell death
Alleles
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Anticarcinogenic Agents - pharmacology
Antimetabolites, Antineoplastic - pharmacology
Antineoplastic agents
Apoptosis
Bax protein
bcl-2-Associated X Protein
bcl-X Protein
Bcl-xL protein
Biological and medical sciences
Cancer
Cell death
Cell lines
Cell physiology
Cells
Chemotherapy
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
DNA
Drug therapy
Epithelial cells
Fluorouracil - pharmacology
Fundamental and applied biological sciences. Psychology
Genes
Genes, p53
Genetic vectors
Genomics
HCT116 cells
Humans
Indomethacin - pharmacology
Intracellular Membranes - drug effects
Intracellular Membranes - physiology
Medical sciences
Membrane Potentials - drug effects
Mitochondria - drug effects
Mitochondria - physiology
Molecular and cellular biology
Mutation
Narcotics
Pathogens
Pharmacology. Drug treatments
Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogenes
Sulindac - pharmacology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - metabolism
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Summary:To assess the role of BAX in drug-induced apoptosis in human colorectal cancer cells, we generated cells that lack functional BAX genes. Such cells were partially resistant to the apoptotic effects of the chemotherapeutic agent 5-fluorouracil, but apoptosis was not abolished. In contrast, the absence of BAX completely abolished the apoptotic response to the chemopreventive agent sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibited the expression of the antiapoptotic protein Bcl-XL, resulting in an altered ratio of BAX to Bcl-XLand subsequent mitochondria-mediated cell death. These results establish an unambiguous role for BAX in apoptotic processes in human epithelial cancers and may have implications for cancer chemoprevention strategies.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.290.5493.989