title: Celecoxib exerts antitumor effects in HL-60 acute leukemia cells and inhibits autophagy by affecting lysosome function.
abstract: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert antitumor activity in a variety of cancer cells. The underlying mechanism involves inhibition of cell cycle progression and induction of apoptosis. Besides, celecoxib has also been found to induce autophagy in some solid tumor cells. The aim of this study was to investigate the effect of celecoxib on cell proliferation in HL-60 human acute leukemia cells and to explore the potential mechanism. HL-60 cells were exposed to various concentrations of celecoxib and cell viability was evaluated by the MTT assay. Apoptosis was analyzed with flow cytometry and the amount of autophagosome was evaluated by LysoTracker probe labelling. The expression of apoptosis- and autophagy-related proteins was assayed by Western blot and LysoSensor probe labelling was used to detect the effect of celecoxib on the lysosomal functions. The results of this study indicated that celecoxib inhibited cell proliferation in a time- and dose-dependent fashion. The flow cytometry analysis showed that celecoxib induced apoptosis at low concentrations and mainly cell necrosis at high concentrations. The Western blot test confirmed the induction of apoptosis by the upregulation of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. Furthermore, this study demonstrated that celecoxib prevented the autophagic flux by inhibiting lysosome function; the fluorescence intensity of the LysoTracker probe and the level of autophagy-related proteins LC3-II and p62 were increased, but the fluorescence intensity of the LysoSensor probe was weakened. These findings show that celecoxib is an autophagy suppresser and has antitumor effects in HL-60 cells by inducing cell apoptosis and necrosis.
authors.affiliation: Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China; Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China.
authors.forename: Xiang-Fu
authors.initials: XF
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Road West, 510630 Guangzhou, PR China.
authors.forename: Ting-Rong
authors.initials: TR
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Fan
authors.affiliation: Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China. Electronic address: bradzxz@126.com.
authors.forename: Xiang-Zhong
authors.initials: XZ
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510630 Guangzhou, PR China. Electronic address: liu600813@163.com.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000068579:Celecoxib / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D009336:Necrosis; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002738:Chloroquine; D000068579:Celecoxib
keywords: AML; Autophagy; Celecoxib