1. Autophagy inhibition enhances daunorubicin-induced apoptosis in K562 cells
- Author
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Kaifeng Wang, Da Li, Qin Pan, Hongming Pan, Yan Chen, Lifeng Feng, Wei Jin, Weidong Han, Jie Sun, Xian Wang, and Hongchuan Jin
- Subjects
Cancer Treatment ,lcsh:Medicine ,Apoptosis ,Signal transduction ,ERK signaling cascade ,Hematologic Cancers and Related Disorders ,Molecular cell biology ,Neoplasms ,Basic Cancer Research ,RNA, Small Interfering ,Extracellular Signal-Regulated MAP Kinases ,lcsh:Science ,health care economics and organizations ,Antibiotics, Antineoplastic ,Microscopy, Confocal ,Multidisciplinary ,Signaling cascades ,Myeloid leukemia ,Chloroquine ,Drug Synergism ,Hematology ,humanities ,Leukemia ,Oncology ,Leukemia, Myeloid ,Antirheumatic Agents ,Medicine ,Research Article ,medicine.drug ,Acute Myeloid Leukemia ,Programmed cell death ,Daunorubicin ,ATG5 ,Chronic Myeloid Leukemia ,Biology ,Microscopy, Electron, Transmission ,Leukemias ,Autophagy ,medicine ,Humans ,Myeloproliferative Disorders ,lcsh:R ,Cancers and Neoplasms ,Chemotherapy and Drug Treatment ,medicine.disease ,Cancer cell ,Cancer research ,lcsh:Q ,K562 Cells ,K562 cells - Abstract
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.
- Published
- 2011