Autophagy inhibition enhances daunorubicin-induced apoptosis in K562 cells

Anthracycline daunorubicin (DNR) is one of the major antitumor agents widely used in the treatment of myeloid leukemia. Unfortunately, the clinical efficacy of DNR was limited because of its cytotoxity at high dosage. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable co...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2011-12, Vol.6 (12), p.e28491
Main Authors: Han, Weidong, Sun, Jie, Feng, Lifeng, Wang, KaiFeng, Li, Da, Pan, Qin, Chen, Yan, Jin, Wei, Wang, Xian, Pan, Hongming, Jin, Hongchuan
Format: Article
Language:English
Subjects:
Activation
Anthracycline
Antibiotics, Antineoplastic - pharmacology
Anticancer properties
Antineoplastic agents
Antirheumatic Agents - pharmacology
Antitumor agents
Apoptosis
Autophagy
B cells
Biology
Biomedical research
Breast cancer
Cancer
Cancer treatment
Carcinogens
Cell death
Chloroquine
Chloroquine - pharmacology
Colorectal cancer
Cytotoxicity
Daunorubicin
Daunorubicin - pharmacology
Deoxyribonucleic acid
DNA
DNA damage
Drug dosages
Drug resistance
Drug Synergism
Extracellular signal-regulated kinase
Extracellular Signal-Regulated MAP Kinases - metabolism
Hospitals
Humans
Immunoglobulins
Inhibition
K562 Cells
Kinases
Laboratories
Leukemia
Leukemia, Myeloid - metabolism
Lung cancer
Medicine
Microscopy, Confocal - methods
Microscopy, Electron, Transmission - methods
Myeloid leukemia
Neoplasms - metabolism
Oncology
Phagocytosis
Pharmacology
Proteins
RNA, Small Interfering - metabolism
Signal Transduction
siRNA
Tumor cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Anthracycline daunorubicin (DNR) is one of the major antitumor agents widely used in the treatment of myeloid leukemia. Unfortunately, the clinical efficacy of DNR was limited because of its cytotoxity at high dosage. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable conditions, autophagy has been proposed to play a role in drug resistance of tumor cells. Whether DNR can activate to impair the sensitivity of cancer cells remains unknown. Here, we first report that DNR can induce a high level of autophagy, which was associated with the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, cell death induced by DNR was greatly enhanced after autophagy inhibition by the pharmacological inhibitor chloroquine (CQ) and siRNAs targeting Atg5 and Atg7, the most important components for the formation of autophagosome. In conclusion, we found that DNR can induce cytoprotective autophagy by activation of ERK in myeloid leukemia cells. Autophagy inhibition thus represents a promising approach to improve the efficacy of DNR in the treatment of patients with myeloid leukemia.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0028491