title: SPARC ectopic overexpression inhibits growth and promotes programmed cell death in acute myeloid leukemia transformed from myelodysplastic syndrome cells, alone and in combination with Ara-C treatment.
abstract: Secreted protein acidic and rich in cysteine (SPARC) has a complex and pleiotropic biological role in cell life during disease. The role of SPARC in myelodysplastic syndrome (MDS) is not yet fully understood. In the present study, we investigated the role of SPARC protein overproduction in the proliferation and apoptosis of SKM-1 cells, an acute myeloid leukemia cell line transformed from MDS. SKM-1 cells were infected with the pGC-GV-SPARC vector. The cells were then assessed for proliferation and cell death following treatment with low-dose cytosine arabinoside (Ara‑C). The microarray analysis results revealed that samples from SPARC‑overexpressed cells compared to SPARC protein, in SKM-1 cells led to proliferation inhibition and promoted programmed cell death and these effects were greater when treated with Ara-C. The mRNA and protein expression levels of SPARC were detected by SPARC overexpression in cells treated with Ara-C resulting in a significant upregulation of the mixed lineage kinase domain-like (MLKL) gene expression and five other genes. The results showed that the necrotic signaling pathway may play a role when the two conditions were combined via the upregulation of the MLKL protein. MLKL upregulation in SPARC overexpressed cells treated with Ara-C, indicates necrosis as a possible cell death process for the SKM-1 cells under these stringent conditions.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Nian
authors.affiliation: The Center for the Study of Haematological Malignancies, Nicosia 2032, Cyprus.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wei
authors.affiliation: The Center for the Study of Haematological Malignancies, Nicosia 2032, Cyprus.
authors.forename: Paul
authors.initials: P
authors.lastname: Costeas
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zesong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009336:Necrosis / Q000235:genetics / Q000473:pathology; D015676:Osteonectin / Q000096:biosynthesis* / Q000235:genetics; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D015676:Osteonectin; C577241:SPARC protein, human; D003561:Cytarabine; C570693:MLKL protein, human; D011494:Protein Kinases