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01-02-2016 | Original Article

Ruxolitinib induces autophagy in chronic myeloid leukemia cells

Authors: Bakiye Goker Bagca, Ozgun Ozalp, Cansu Caliskan Kurt, Zeynep Mutlu, Guray Saydam, Cumhur Gunduz, Cigir Biray Avci

Published in: Tumor Biology | Issue 2/2016

Abstract

Ruxolitinib is the first agent used in myelofibrosis treatment with its potent JAK2 inhibitory effect. In this novel study, we aimed to discover the anti-leukemic effect of ruxolitinib in K-562 human chronic myeloid leukemia cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Cytotoxic effect of ruxolitinib was determined by using WST-1 assay. IC₅₀ values for K-562 and NCI-BL 2171 cell lines were defined as 20 and 23.6 μM at the 48th hour, respectively. Autophagic effects of ruxolitinib were detected by measuring LC3B-II protein formation. Ruxolitinib induced autophagic cell death in K-562 and NCI-BL 2171 cell lines 2.11- and 1.79-fold compared to control groups, respectively. To determine the autophagy-related gene expression changes, total RNA was isolated from K-562 and NCI-BL 2171 cells treated with ruxolitinib and untreated cells as control group. Reverse transcription procedure was performed for cDNA synthesis, and gene expressions were shown by RT-qPCR. Ruxolitinib treatment caused a notable decrease in expression of AKT, mTOR, and STAT autophagy inhibitor genes in K-562 cells, contrariwise control cell line. Ruxolitinib is a promising agent in chronic myeloid leukemia treatment by blocking JAK/STAT pathway known as downstream of BCR-ABL and triggering autophagy. This is the first study that reveals the relationship between ruxolitinib and autophagy induction.

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Title: Ruxolitinib induces autophagy in chronic myeloid leukemia cells
Authors: Bakiye Goker Bagca
Ozgun Ozalp
Cansu Caliskan Kurt
Zeynep Mutlu
Guray Saydam
Cumhur Gunduz
Cigir Biray Avci
Publication date: 01-02-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3947-4

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