@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 {1769,
	title = {Activation of the p53 pathway induces α-smooth muscle actin expression in both myeloid leukemic cells and normal macrophages.},
	journal = {J Cell Physiol},
	volume = {227},
	year = {2012},
	month = {2012 May},
	pages = {1829-37},
	abstract = {<p>A range of cell types of mesenchymal origin express α-smooth muscle actin (α-SMA), a protein that plays a key role in controlling cell motility and differentiation along the fibrocyte and myofibroblast lineages. Although α-SMA is often expressed in stromal cells associated to a variety of cancers including hematological malignancies, up to now the role of anti-cancer drugs on α-SMA has not been deeply investigated. In this study, we demonstrated that Nutlin-3, the small molecule inhibitor of the MDM2/p53 interactions, significantly up-regulated the mRNA and protein levels of α-SMA in normal macrophages as well as in p53(wild-type) but not in p53(mutated/null) myeloid leukemic cells. The p53-dependence of α-SMA up-regulation induced by Nutlin-3 was demonstrated in experiments performed with siRNA for p53. Of note, Nutlin-3 mediated up-regulation of α-SMA in OCI leukemic cells was accompanied by cell adhesion to plastic substrate and by reduced cell migratory response in transwell assays. Notably, the role of α-SMA induction in the modulation of myeloid cell migration was clearly documented in α-SMA gene knockdown experiments. In addition, Nutlin-3 significantly up-regulated α-SMA expression in primary endothelial cells, but not in fibroblasts and mesenchymal stem cells (MSC). Conversely, transforming growth factor-β1 up-regulated α-SMA in fibroblasts and MSC, but not in macrophages and endothelial cells. Taken together, these data indicate that Nutlin-3 is a potent inducer of α-SMA in both normal and leukemic myeloid cells as well as in endothelial cells.</p>},
	keywords = {Actins, Cell Movement, Cells, Cultured, Endothelial Cells, Fibroblasts, Humans, Imidazoles, Leukemia, Myeloid, Macrophages, Mesenchymal Stromal Cells, Piperazines, Proto-Oncogene Proteins c-mdm2, RNA, Small Interfering, Signal Transduction, Transforming Growth Factor beta1, Tumor Suppressor Protein p53},
	issn = {1097-4652},
	doi = {10.1002/jcp.22910},
	author = {Secchiero, Paola and Rimondi, Erika and di Iasio, Maria Grazia and Voltan, Rebecca and Gonelli, Arianna and Zauli, Giorgio}
}
