The Michelakis Paper/title>  <meta name=robots content="index,follow"> <meta name="robots" content="all"> <meta name="verify-v1" content="mgsp11K0wX1bbYCpJoNceiRzfY3bimiuLVhG8OLhaWA=" /> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <style type="text/css">  </style> <link href="style.css" rel="stylesheet" type="text/css">  </head> <body leftmargin="0" topmargin="0" marginwidth="0" marginheight="0"> <table width="837" border="0" cellspacing="0" cellpadding="0"> <tr> <td valign="top"><img src="images/DCA_site_01.jpg" width="837" height="48" alt=""></td> </tr> <tr> <td valign="top"><img src="images/DCA_site_02.jpg" width="172" height="100" alt="DCA and Cancer"><img src="images/DCA_site_03.jpg" width="618" height="100" alt="DCA as a Cancer Treatment - Sodium Dichloroacetate"><img src="images/DCA_site_04.jpg" width="47" height="100" alt=""></td> </tr> <tr> <td valign="top"><img src="images/DCA_site_05.jpg" width="837" height="22" alt=""></td> </tr> <tr> <td valign="top"><table width="837" border="0" cellspacing="0" cellpadding="0"> <tr> <td width="34" valign="top" background="images/leftbar.jpg"><img src="images/spacer.gif" width="34" height="100"></td> <td width="125" valign="top" bgcolor="#FFFFFF"><table width="125" border="0" cellspacing="0" cellpadding="1"> <tr> <td valign="top" class="menu"><a href="index.html">Home</a></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p class="menu"><a href="the_dca_papers.html">The DCA Papers</a> </p></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p><a href="the_dca_patents.html">The DCA Patents </a></p></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p><a href="dca_how_it_works.html">DCA & How it Works</a> </p></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p><a href="dca_human_studies.html">DCA Human Studies </a></p></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p><a href="DCA-Related_Animal_Studies.html">DCA Animal Studies</a></p></td> </tr> <tr> <td valign="top" class="menu"><img src="images/menudiv.gif" width="123" height="7"></td> </tr> <tr> <td valign="top" class="menu"><p><a href="dca_commentary.html">Commentary - 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Archer1, 2, Joan Allalunis-Turner3, Alois Haromy1, Christian Beaulieu4, Richard Thompson4, Christopher T. Lee5, Gary D. Lopaschuk5, 6, Lakshmi Puttagunta7, Sandra Bonnet1, Gwyneth Harry1, Kyoko Hashimoto1, Christopher J. Porter8, Miguel A. Andrade8, Bernard Thebaud1, 6 and Evangelos D. Michelakis1, , <br> 1Pulmonary Hypertension Program and Vascular Biology Group, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 2Department of Physiology, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 3Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 4Department of Biomedical Engineering, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 5Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 6Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 7Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada<br> 8Ontario Genomics Innovation Centre, Ottawa Health Research Institute, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada <br> Received 25 November 2005; revised 12 July 2006; accepted 18 October 2006. Published: January 15, 2007. Available online 16 January 2007. </p> <p> </p> <p align="left"><strong>Abstract</strong></p> <p>The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (ΔΨm) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases ΔΨm, 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 inhibits tumor growth, 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 promising selective anticancer agent. </p> <p align="left"> </p> <p align="left"> </p> <p align="left">.</p> <p class="body"><a href="#top">top</a></p>  <p> </p></td> <td width="62" valign="top" background="images/DCA_site_10.jpg"><img src="images/spacer.gif" width="62" height="100"></td> </tr> </table></td> </tr> <tr> <td valign="top"><img src="images/DCA_site_111.jpg" width="837" height="73" alt="DCA"></td> </tr> <tr> <td align="center" valign="top" class="menu"><a href="http://levelonewebdesign.com/" target="_blank">web design by LevelOneWebDesign.com</a> </td> </tr> </table> <p> </p> <p> </p> </body> </html>