Influence of arsenic trioxide on the expression of cyclin A in the Jurkat cel line

A. Żuryń, Magdalena Czołpińska, Adrian Krajewski, A. Litwiniec, Anna Klimaszewska-Wiśniewska, A. Grzanka
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Abstract

Improper expression of cell cycle regulators is characteristic for most cancer cells. Cyclins are a group of proteins, with concentration changing in time, which control progression through each phase of the cell cycle. Maximum cyclin A expression falls inside S and at the beginning of M phase. In the S phase cyclin A is responsible for a proper run of the replication process, and together with cyclin B conditions transition into the M phase. Arsenic trioxide (ATO) is an efficient drug used in acute promyelocytic leukemia (AML). Numerous reports point that arsenic trioxide can be applied in therapy of other types of cancer as well. The purpose of these study was to evaluate influence of arsenic trioxide on the expression and localization of cyclin A in Jurkat cell line. Additionally, we determined the effect of ATO on morphology and ultrastructure of the Jurkat cells. In order to reach this aim we applied classic light, florescence and electron transmission microscopy. A dose-dependent decrease in the percentage of viable cells was observed. Morphological and ultrastructural alterations suggest that apoptosis and autophagy are induced by ATO. Image-based cytometry showed high extent of necrotic cells after ATO treatment. A decrease in cyclin A level was observed, but without a change in protein nuclear localization.
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三氧化二砷对Jurkat细胞系细胞周期蛋白A表达的影响
细胞周期调节因子的不正确表达是大多数癌细胞的特征。细胞周期蛋白是一组浓度随时间变化的蛋白质,它控制着细胞周期的每个阶段的进展。cyclin A在S期和M期开始时表达量最大。在S期,周期蛋白A负责复制过程的正常运行,并与周期蛋白B一起过渡到M期。三氧化二砷(ATO)是治疗急性早幼粒细胞白血病(AML)的有效药物。许多报告指出,三氧化二砷也可用于治疗其他类型的癌症。本研究旨在探讨三氧化二砷对Jurkat细胞株细胞周期蛋白A表达和定位的影响。此外,我们还测定了ATO对Jurkat细胞形态和超微结构的影响。为了达到这一目的,我们应用了经典光、荧光和电子透射显微镜。观察到活细胞百分比呈剂量依赖性下降。形态学和超微结构改变提示ATO可诱导细胞凋亡和自噬。图像细胞术显示ATO处理后细胞高度坏死。观察到细胞周期蛋白A水平下降,但蛋白核定位没有改变。
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