Evaluation of Effect of As2O3 on Cell Growth, Cell Cycle and Apoptosis in Human Leukemia Cell Line HL-60
Shahrbano Rostami, Saeid Abroun, K. Alimoghaddam, Mehrdad Nourozinia, Bahram Chahardouli, Ardeshir Ghavamzade
Abstract
Shahrbano Rostami, Saeid Abroun, K. Alimoghaddam, Mehrdad Nourozinia, Bahram Chahardouli, Ardeshir Ghavamzade
Abstract
Introduction: Arsenic Trioxide (As2O3) causes antitumor effects by various mechanisms, including degradation of PML-RARA in the acute promyelocytic cells, growth inhibition and induction of apoptosis. However, the precise mechanisms of these processes remain incompletely understood. The purpose of this study was to evaluate the effects of arsenic trioxide on cell growth, cell cycle regulation and apoptosis in PML/RARA negative acute promyelocytic leukemia cell line HL-60.Methods: The cytotoxic effect of As2O3 was assessed by MTT assay, Apoptosis was detected by flow cytometry analysis using annexin V–FITC/PI and cell cycle distribution was evaluated by propidium iodide staining.Results: MTT assay showed that cell growth was inhibited in a time- and dose-dependent manner. As2O3 exerts growth inhibitory effect by arresting the cells at G2/M phase. Apoptosis analysis revealed that As2O3 treatment induced apoptosis at the lower concentrations, while necrosis occurred at the higher concentrations.Conclusion: As2O3 inhibits growth and induces apoptosis of HL-60 cells through induction of cell cycle arrest. Further studies are required to elucidate the molecular mechanisms of As2O3-induced anti-tumor effects.
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Introduction: Arsenic Trioxide (As2O3) causes antitumor effects by various mechanisms, including degradation of PML-RARA in the acute promyelocytic cells, growth inhibition and induction of apoptosis. However, the precise mechanisms of these processes remain incompletely understood. The purpose of this study was to evaluate the effects of arsenic trioxide on cell growth, cell cycle regulation and apoptosis in PML/RARA negative acute promyelocytic leukemia cell line HL-60.Methods: The cytotoxic effect of As2O3 was assessed by MTT assay, Apoptosis was detected by flow cytometry analysis using annexin V–FITC/PI and cell cycle distribution was evaluated by propidium iodide staining.Results: MTT assay showed that cell growth was inhibited in a time- and dose-dependent manner. As2O3 exerts growth inhibitory effect by arresting the cells at G2/M phase. Apoptosis analysis revealed that As2O3 treatment induced apoptosis at the lower concentrations, while necrosis occurred at the higher concentrations.Conclusion: As2O3 inhibits growth and induces apoptosis of HL-60 cells through induction of cell cycle arrest. Further studies are required to elucidate the molecular mechanisms of As2O3-induced anti-tumor effects.
Key concepts: Arsenic trioxide, Propidium iodide, Apoptosis, Acute promyelocytic leukemia, Cell cycle, Annexin, Cell growth, MTT assay