RITA induces apoptosis in p53-null K562 leukemia cells by inhibiting STAT5, Akt, and NF-κB signaling pathways

Anti-cancer Drugs
Rashideh N MobarakiMajid Safa

Abstract

Targeting oncogenic signaling pathways by small molecules has emerged as a potential treatment strategy for cancer. reactivation of p53 and induction of tumor cell apoptosis (RITA) is a promising anticancer small molecule that reactivates p53 and induces exclusive apoptosis in tumor cells. Less well appreciated was the possible effect of small molecule RITA on p53-null leukemia cells. In this study, we demonstrated that RITA has potent antileukemic properties against p53-null chronic myeloid leukemia (CML)-derived K562 cells. RITA triggered apoptosis through caspase-9 and caspase-3 activation and poly (ADP-ribose) polymerase cleavage. RITA decreased STAT5 tyrosine phosphorylation, although it did not inhibit phosphorylation of the direct BCR-ABL substrate CrkL. Real-time PCR analysis showed that RITA downregulates antiapoptotic STAT5 target genes Bcl-xL and MCL-1. The downregulation of nuclear factor-κB (NF-κB), as evidenced by inhibition of IκB-α phosphorylation and its degradation, was associated with inhibition of Akt phosphorylation in RITA-treated cells. Furthermore, consistent with the decrease of mRNA levels, protein levels of the nuclear factor-κB-regulated antiapoptotic (cIAP1, XIAP, and Bcl-2) and proliferative (c-Myc...Continue Reading

References

Jan 1, 1993·Leukemia & Lymphoma·C L Sawyers
May 9, 1998·Genes & Development·J Y ReutherA S Baldwin
Nov 10, 2000·European Journal of Haematology·R SaffroyB Debuire
Mar 1, 2002·The New England Journal of Medicine·David G Savage, Karen H Antman
Jun 28, 2003·Experimental Hematology·Dieter KirchnerGerd Munzert
Sep 20, 2005·Cancer Cell·Nissim Hay
Mar 18, 2006·Cell Death and Differentiation·J E Chipuk, D R Green
Aug 25, 2007·Cellular Signalling·Arnaud ParcellierBrian A Hemmings
Jan 1, 2009·Nature Reviews. Drug Discovery·Véronique Baud, Michael Karin
Mar 5, 2010·EMBO Molecular Medicine·Andrea HoelblVeronika Sexl
Jan 31, 2012·Nature Chemical Biology·Oliver HantschelVeronika Sexl
Aug 30, 2014·Blood·Peter Valent
Feb 15, 2015·EMBO Reports·Raymond PagliariniWilliam R Sellers
Jun 10, 2016·Nature·Sheela A AbrahamTessa L Holyoake

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Citations

Feb 6, 2020·Fundamental & Clinical Pharmacology·Higor de Oliveira RibeiroMarize Campos Valadares
Sep 5, 2019·Apoptosis : an International Journal on Programmed Cell Death·Ewa Jasek-GajdaGrzegorz J Lis

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
PCR
flow cytometry
electrophoresis

Software Mentioned

CellQuest

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