Cancer Letters
Volume 297, Issue 1 , Pages 75-83, 1 November 2010

Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia

Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1

Received 20 January 2010; received in revised form 6 April 2010; accepted 15 April 2010. published online 31 May 2010.

Abstract 

We examined the effect of hypoxia on apoptosis of human colorectal cancer (CRC) cells in vitro and in vivo. All cell lines tested were susceptible to hypoxia-induced apoptosis. DCA treatment caused significant apoptosis under normoxia in SW480 and Caco-2 cells, but these cells displayed decreased apoptosis when treated with DCA combined with hypoxia, possibly through HIF-1α dependent pathways. DCA treatment also induced significantly increased growth of SW480 tumor xenografts, and a decrease in TUNEL positive nuclei in hypoxic but not normoxic regions of treated tumors. Thus DCA is cytoprotective to some CRC cells under hypoxic conditions, highlighting the need for further investigation before DCA can be used as a reliable apoptosis-inducing agent in cancer therapy.

Abbreviations: CRC, colorectal cancer, DCA, dichloroacetate, HIF, hypoxia inducible factor

Keywords: Dichloroacetate, Colorectal cancer, Apoptosis, Hypoxia, Tumor microenvironment

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PII: S0304-3835(10)00251-X

doi:10.1016/j.canlet.2010.04.027

Cancer Letters
Volume 297, Issue 1 , Pages 75-83, 1 November 2010

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