title: Ruxolitinib induces autophagy in chronic myeloid leukemia cells.
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.
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey. goker.bb@gmail.com.
authors: Bakiye Goker
authors: BG
authors: Bagca
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey.
authors: Ozgun
authors: O
authors: Ozalp
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey.
authors: Cansu Caliskan
authors: CC
authors: Kurt
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey.
authors: Zeynep
authors: Z
authors: Mutlu
authors: Department of Hematology, School of Medicine, Ege University, Izmir, Turkey.
authors: Guray
authors: G
authors: Saydam
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey.
authors: Cumhur
authors: C
authors: Gunduz
authors: Department of Medical Biology, School of Medicine, Ege University, Izmir, Turkey.
authors: Cigir Biray
authors: CB
authors: Avci
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D009570:Nitriles; D016133:Polymerase Chain Reaction; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib
keywords: Autophagy; Chronic myeloid leukemia; JAK/STAT pathway; Ruxolitinib