@article {7729,
	title = {The anti-leukemic activity of sodium dichloroacetate in p53mutated/null cells is mediated by a p53-independent ILF3/p21 pathway.},
	journal = {Oncotarget},
	volume = {6},
	year = {2015},
	month = {2015 Feb 10},
	pages = {2385-96},
	abstract = {<p>B-chronic lymphocytic leukemia (B-CLL) patients harboring p53 mutations are invariably refractory to therapies based on purine analogues and have limited treatment options and poor survival. Having recently demonstrated that the mitochondria-targeting small molecule sodium dichloroacetate (DCA) exhibits anti-leukemic activity in p53wild-type B-CLL cells, the aim of this study was to evaluate the effect of DCA in p53mutated B-CLL cells and in p53mutated/null leukemic cell lines. DCA exhibited comparable cytotoxicity in p53wild-type and p53mutated B-CLL patient cell cultures, as well as in p53mutated B leukemic cell lines (MAVER, MEC-1, MEC-2). At the molecular level, DCA promoted the transcriptional induction of p21 in all leukemic cell types investigated, including p53null HL-60. By using a proteomic approach, we demonstrated that DCA up-regulated the ILF3 transcription factor, which is a known regulator of p21 expression. The role of the ILF3/p21 axis in mediating the DCA anti-leukemic activity was underscored by knocking-down experiments. Indeed, transfection with ILF3 and p21 siRNAs significantly decreased both the DCA-induced p21 expression and the DCA-mediated cytotoxicity. Taken together, our results emphasize that DCA is a small molecule that merits further evaluation as a therapeutic agent also for p53mutated leukemic cells, by acting through the induction of a p53-independent pathway.</p>},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.2960},
	author = {Agnoletto, Chiara and Brunelli, Laura and Melloni, Elisabetta and Pastorelli, Roberta and Casciano, Fabio and Rimondi, Erika and Rigolin, Gian Matteo and Cuneo, Antonio and Secchiero, Paola and Zauli, Giorgio}
}
@article {3581,
	title = {Sodium dichloroacetate exhibits anti-leukemic activity in B-chronic lymphocytic leukemia (B-CLL) and synergizes with the p53 activator Nutlin-3.},
	journal = {Oncotarget},
	volume = {5},
	year = {2014},
	month = {2014 Jun 30},
	pages = {4347-60},
	abstract = {<p>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. 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.</p>},
	keywords = {Aged, Aged, 80 and over, Dichloroacetic Acid, Drug Synergism, Female, Humans, Imidazoles, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Piperazines, Tumor Suppressor Protein p53},
	issn = {1949-2553},
	author = {Agnoletto, Chiara and Melloni, Elisabetta and Casciano, Fabio and Rigolin, Gian Matteo and Rimondi, Erika and Celeghini, Claudio and Brunelli, Laura and Cuneo, Antonio and Secchiero, Paola and Zauli, Giorgio}
}
