| In vitro: |
| Cancer Lett. 2010 Nov 1;297(1):75-83. | | Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia.[Pubmed: 20537792 ] |
METHODS AND RESULTS:
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. Sodium Dichloroacetate (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-1alpha 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.
CONCLUSIONS:
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. | | Oncotarget. 2014 Jun; 5(12): 4347–4360. | | Sodium dichloroacetate exhibits anti-leukemic activity in B-chronic lymphocytic leukemia (B-CLL) and synergizes with the p53 activator Nutlin-3[Pubmed: 24962518 ] |
METHODS AND RESULTS:
The anti-leukemic activity of the mitochondria-targeting small molecule Sodium Dichloroacetate (DCA), used alone and in association with the small molecule inhibitor of the p53/MDM2 interaction Nutlin-3, was analyzed in primary B-chronic lymphocytic leukemia (B-CLL) samples (n=22), normal peripheral blood cells (n=10) and in p53wild-type EHEB, JVM-2, JVM-3 B lymphoblastoid cell lines. DCA exhibited a dose-dependent anti-leukemic activity in both primary B-CLL and B leukemic cell lines with a functional p53 status and showed a synergistic cytotoxic activity when used in combination with Nutlin-3. At the molecular level, DCA positively regulated p53 activity, as documented by post-transcriptional modifications of p53 protein, and synergized with Nutlin-3 in increasing the expression of the p53-target genes MDM2, PUMA, TIGAR and in particular p21. The potential role of p21 in mediating the DCA+Nutlin-3 anti-leukemic activity was underscored in knocking-down experiments. Indeed, transfection of leukemic cells with p21 siRNAs significantly decreased the DCA+Nutlin-3-induced cytotoxicity.
CONCLUSIONS:
Taken together, our data emphasize that DCA is a molecule that merits to be further evaluated as a chemotherapeutic agent for B-CLL, likely in combination with other therapeutic compounds. |
|
| In vivo: |
| Fundam Appl Toxicol. 1996 Jul;32(1):87-95. | | Absence of mutagenic effects of sodium dichloroacetate.[Pubmed: 8812237] | Sodium dichloroacetate (DCA) is a drug with potential for treating patients with stroke and head injury. Conflicting evidence has been published on the mutagenic potential of DCA.
METHODS AND RESULTS:
A series of genetic tests for mutagenicity and clastogenicity was carried out on pharmaceutical grade DCA. Four types of mutagenicity test were included, with and without metabolic activation where appropriate. These studies included: (i) Salmonella and Escherichia coli mutation (Ames) test, (ii) thymidine kinase locus forward mutation in L5178Y mouse lymphoma cells, (iii) tests for chromosomal aberrations in Chinese hamster ovary cells, and (iv) and in vivo rat bone marrow erythroid micronucleus test. In each study, there was no evidence of mutagenic activity attributable to DCA. It is possible that the present test material, of pharmaceutical grade, has fewer impurities than materials studied in previous reports.
CONCLUSIONS:
These data extend, and in some cases contradict, previous published reports on DCA. |
|
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