Sodium dichloroacetate (DCA)
Catalog No.S8615 Synonyms: bichloroacetic acid, BCA
Molecular Weight(MW): 150.92
Dichloroacetate, a specific inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50 values of 183 and 80 μM for PDK2 and PDK4 respectively, has been shown to derepress a mitochondrial potassium-ion channel axis, trigger apoptosis in cancer cells, and inhibit tumor growth.
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|Description||Dichloroacetate, a specific inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50 values of 183 and 80 μM for PDK2 and PDK4 respectively, has been shown to derepress a mitochondrial potassium-ion channel axis, trigger apoptosis in cancer cells, and inhibit tumor growth.|
DCA can trigger apoptosis of human lung, breast and brain cancer cells. After DCA treatment, cancer cells shows increased levels of ROS, depolarization of the MMP in vitro and increased apoptosis both in vitro and in vivo. DCA inhibits the activity of pyruvate dehydrogenase kinase (PDK), thereby stimulating the mitochondrial enzyme pyruvate dehydrogenase (PDH). When turned off, PDH no longer converts pyruvate to acetyl-CoA required for mitochondrial respiration and glucose dependent oxidative phosphorylation. DCA thus shifts cellular metabolism from glycolysis to glucose oxidation, decreasing the mitochondrial membrane potential gradient and helping to open mitochondrial transition pores. This metabolic switch facilitates translocation of pro-apoptotic mediators like cytochrome c (cyt c) and apoptosis inducing factor (AIF), both of which stimulate apoptosis. DCA thereby drives cancer cells to commit suicide by apoptosis.
|In vivo||DCA can act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). DCA is discovered to be a safe drug with no cardiac, pulmonary, renal or bone marrow toxicity. The most serious common side effect consists of peripheral neuropathy, which is reversible. DCA has anti-cancer activity in several cancer types including colon, prostate, ovarian, neuroblastoma, lung carcinoid, cervical, endometrial, cholangiocarcinoma, sarcoma and T-cell lymphoma. Other antineoplastic actions of DCA have also been suggested. These include angiogenesis blockade, changes in expression of HIF1-α, alteration of pH regulators V-ATPase and MCT1, and other cell survival regulators such as PUMA, GLUT1, Bcl2 and p53. DCA is able to significantly reduce metastatic burden in the lungs of rats in a highly metastatic in vivo model of breast cancer. In vivo the DCA-Na treatment induces 20% survival and decreased the tumoral diameter, volume and weight, without affect the body weight and avoid metastasis in C57BL/6 mice.|
|In vitro||DMSO||30 mg/mL (198.78 mM)|
|Water||30 mg/mL (198.78 mM)|
|Ethanol||30 mg/mL (198.78 mM)|
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
|Synonyms||bichloroacetic acid, BCA|
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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01386632||Active not recruiting||Squamous Cell Carcinoma of the Head and Neck||Sanford Health||May 2011||Phase 2|
|NCT01111097||Completed||Brain Tumor|Glioblastoma||University of Florida|National Institutes of Health (NIH)||April 2010||Phase 1|
|NCT01083524||Completed||Pulmonary Hypertension (Idiopathic Familial or Anorexigen-associated)||University of Alberta|Imperial College London||March 2010||Phase 1|
|NCT01029925||Terminated||Metastatic Breast Cancer|Lung Cancer||Jonsson Comprehensive Cancer Center||December 2009||Phase 2|
|NCT00566410||Completed||Neoplasms||AHS Cancer Control Alberta|Cross Cancer Institute||December 2007||Phase 1|
|NCT00540176||Completed||Malignant Gliomas Glioblastoma Multiforme||University of Alberta|Capital Health Canada||October 2007||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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