title: [Effect of Artesunate on Proliferation, Cell Cycle and Apoptosis of SKM-1 Cells and Its Underlying Mechanisms].
abstract: OBJECTIVE
  To investigate the effects of artesunate (ART) on proliferation, cell cycle and apoptosis of SKM-1 cells in vitro and to explore the underlying mechanisms.
  
  
  METHODS
  After SKM-1 cells were treated with different concentrations of ART, the cell proliferation was determined by CCK-8 method. Apoptosis and distribution of cell cycle were detected by flow cytometry. Both DCFH-DA fluorescent probe and Fluo-3-Am fluorescent probe were used to detect the changes of intracellular reactive oxygen species (ROS) and calcium ion concentration. Western blot was used to measure the protein levels of BCL-2, BAX, BAD, P-BAD, survivin and XIAP.
  
  
  RESULTS
  ART obviously inhibited the growth of SKM-1 cells in time and dose-dependent manners (r = -0.841; r = 0.-786). The antioxidant trolox-pretreatment significantly decreased the growth inhibition effect of ART on SKM-1 cells. Caspase inhibitor Ac-DEVD-CHO partially reduced the growth inhibition effect of ART on SKM-1 cells. After treatment with ART for 24 hours, the apoptosis of SKM-1 cells was found, the cell cycle of SKM-1 was arrested in G0/G1 phase, ART could elevate the levels of calciumion and reactive orygen. ART could significantly down-regulate the protein expression levels of P-BAD and survivin in SKM-1 cells, and showed a highly negative correlation with ART dose (r = -0.909; r = -0.849). On the contrary, ART had no significant effect on expression levels of BAD and XIAP in SKM-1 cells, and after ART treatment, although BCL-2 protein expression was not significantly different when compared with control group, but the BCL-2/BAX ratio significantly decreased and highly negatively correlated with ART dose (r = -0.866).
  
  
  CONCLUSIONS
  The ART significantly suppresses the cell proliferation, induces the apoptosis and promoted cell cycle arrest at G0/G1 phase in SKM-1 cells. The mechanisms of ART anti-MDS is associated with the increase of intracellular calciumion concentration and ROS levels. In addition, the pro-apoptotic activity of ART may be involved in the regulation of BCL-2 /BAX ratio and the expressions of P-bad and survivin.
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University; Shijiazhuang 050000, Hebei Province, China.
authors.forename: Shu-Kai
authors.initials: SK
authors.lastname: Qiao
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University; Shijiazhuang 050000, Hebei Province, China. E-mail: wangying730@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University; Shijiazhuang 050000, Hebei Province, China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Niu
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University; Shijiazhuang 050000, Hebei Province, China.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Tan
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University; Shijiazhuang 050000, Hebei Province, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037621:Artemisinins; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D000077332:Artesunate; D002118:Calcium