title: Proapoptotic effects of heme oxygenase-1 inhibitor on Kasumi-1 cells via the ATF4/CHOP/Ire-1α pathway.
abstract: We evaluated the effects of down-regulated heme oxygenase (HO)-1 expression on the proliferation of the acute myelocytic leukemia Kasumi-1 cell line by using the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) in combination with daunorubicin (DNR), and evaluated the mechanism. The proliferation rates of cells treated with 10 mg/mL DNR and 10 mM ZnPPIX individually or in combination for different time periods were detected using the MTT assay. The apoptotic outcomes of the blank control, ZnPPIX, DNR, and ZnPPIX groups in combination with the DNR group were detected by flow cytometry. The expression of HO-1, activating transcription factor 4, CCAAT-enhancer-binding protein homologous protein, and inositol-requiring enzyme-α mRNA and proteins were detected by fluorescent quantitative real-time polymerase chain reaction and western blotting, respectively. Combined administration inhibited the cells most potently and time-dependently, decreased the expression of HO-1, and significantly increased the expression of activating transcription factor 4, CCAAT-enhancer-binding protein homologous protein, and inositol-requiring enzyme-α expression levels. The cell apoptotic rates in the blank control, DNR, ZnPPIX, and combined administration groups were 8.32 ± 0.53, 39.16 ± 1.46, 10.46 ± 0.88, and 56.26 ± 2.24%, respectively. Inhibiting HO-1 expression can enhance the damaging effects of DNR on Kasumi-1 cells, providing experimental evidence for the improvement of therapeutic effects on acute myelocytic leukemia in clinical practice.
authors.affiliation: Department of Hematology, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors.forename: S-X
authors.initials: SX
authors.lastname: Wei
authors.affiliation: Department of Blood Transfusion, People's Hospital of Yuxi, Yuxi, China.
authors.forename: Y-T
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Hematology, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors.forename: Q-X
authors.initials: QX
authors.lastname: Chai
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Hematology, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated Hospital of Guiyang Medical College, Guiyang, China jishiwangcn@163.com.
authors.forename: J-S
authors.initials: JS
authors.lastname: Wang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004722:Endoribonucleases / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C497109:ATF4 protein, human; C497249:DDIT3 protein, human; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D051547:Heme Oxygenase-1; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases