Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells.
Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23-induced up-regulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards.
Cocco
Claudia
C
Associazione Italiana per Ricerca sul Cancro Laboratory of Immunology and Tumors, Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genova, Italy.
Canale
Sara
S
Frasson
Chiara
C
Di Carlo
Emma
E
Ognio
Emanuela
E
Ribatti
Domenico
D
Prigione
Ignazia
I
Basso
Giuseppe
G
Airoldi
Irma
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology
C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D011994:Recombinant Proteins