title: Autophagy inhibition enhances daunorubicin-induced apoptosis in 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.
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Lifeng
authors.initials: L
authors.lastname: Feng
authors.forename: KaiFeng
authors.initials: K
authors.lastname: Wang
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D002738:Chloroquine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009369:Neoplasms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000903:Antibiotics, Antineoplastic; D018501:Antirheumatic Agents; D034741:RNA, Small Interfering; D002738:Chloroquine; D048049:Extracellular Signal-Regulated MAP Kinases; D003630:Daunorubicin