Ruxolitinib induces autophagy in chronic myeloid leukemia cells


Bagca B. G. , ÖZALP O., Kurt C. C. , MUTLU Z., SAYDAM G. , GÜNDÜZ C. , et al.

TUMOR BIOLOGY, cilt.37, ss.1573-1579, 2016 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 37 Konu: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1007/s13277-015-3947-4
  • Dergi Adı: TUMOR BIOLOGY
  • Sayfa Sayısı: ss.1573-1579

Özet

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 mu M 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.