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Tumor Biology

, Volume 37, Issue 2, pp 1573–1579 | Cite as

Ruxolitinib induces autophagy in chronic myeloid leukemia cells

  • Bakiye Goker Bagca
  • Ozgun Ozalp
  • Cansu Caliskan Kurt
  • Zeynep Mutlu
  • Guray Saydam
  • Cumhur Gunduz
  • Cigir Biray Avci
Original Article

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.

Keywords

Ruxolitinib Chronic myeloid leukemia Autophagy JAK/STAT pathway 

Notes

Acknowledgments

This study was supported by the Research Foundation of Ege University Medical School (Grant Number 2014/TIP/048).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Bakiye Goker Bagca
    • 1
  • Ozgun Ozalp
    • 1
  • Cansu Caliskan Kurt
    • 1
  • Zeynep Mutlu
    • 1
  • Guray Saydam
    • 2
  • Cumhur Gunduz
    • 1
  • Cigir Biray Avci
    • 1
  1. 1.Department of Medical Biology, School of MedicineEge UniversityIzmirTurkey
  2. 2.Department of Hematology, School of MedicineEge UniversityIzmirTurkey

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