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| Status |
Public on Oct 11, 2006 |
| Title |
A Mitochondria-K+ Channel Axis Is Suppressed in Cancer & Its Normalization Promotes Apoptosis and Inhibits Cancer Growth |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a novel selective anticancer agent.
Keywords: treatment
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| Overall design |
lung carcinoma and brain glioblastoma cells were analalyzed, with microarrays run both for control and treatment with DCA
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| Contributor(s) |
Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade-Navarro MA, Thebaud B, Michelakis ED |
| Citation(s) |
17222789 |
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| Submission date |
Oct 11, 2006 |
| Last update date |
Aug 10, 2018 |
| Organization |
Ottawa Hospital Research Institute |
| Phone |
(613) 737-8899 -73255
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| Department |
Cellular and Molecular Medicine
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| Lab |
Ottawa Bioinformatics Core Facility
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| Street address |
501 Smyth Rd.
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| City |
Ottawa |
| State/province |
ON |
| ZIP/Postal code |
K1H 8L6 |
| Country |
Canada |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (4)
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| GSM139670 |
A549DCA: DCA treated lung carcinoma cells |
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| Relations |
| BioProject |
PRJNA97815 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE6014_RAW.tar |
12.4 Mb |
(http)(custom) |
TAR (of CEL) |
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