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Acute Promyelocytic Leukemia and AS203

Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells

Leukemia volume 17, pages 1333–1337 (2003)Cite this article

Abstract

Arsenic trioxide (As2O3), an effective drug for the treatment of acute promyelocytic leukemia (APL), can induce apoptosis and partial differentiation in APL cells in vitro and in vivo. However, As2O3 also induces apoptosis in cancer cells other than APL with complex mechanisms, which seem to be cell type dependent. In this study, we report that APL cells (NB4 cell line) are arrested at early mitotic phase before the collapse of mitochondrial transmembrane potential (Δϕm) and apoptosis after treatment with pharmacological concentrations (1.0–2.0 μ M) of As2O3. We have also made the following new discoveries: (1) 0.5 μ M As2O3 that fails to induce apoptosis has no effects on cell cycle distribution. (2) With inhibition of As2O3-induced Δϕm collapse and apoptosis, dithiothreitol also effectively inhibits As2O3-induced mitotic arrest, suggesting that both As2O3-induced apoptosis and mitotic arrest involve proteins with thiol groups. (3) 1.5 mM caffeine that relieves cells from G2/M arrest also inhibits As2O3-induced Δϕm collapse and apoptosis, (4) 1.0 μ M As2O3 increases the expression of both cyclin B1 and hCDC20 whereas it inhibits Tyr15 phosphorylation of p34cdc2. In conclusion, our results strongly support that there is a tight link between As2O3-induced apoptosis and mitotic arrest, the latter being one of common mechanisms for As2O3-induced apoptosis in cancer cells.

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Acknowledgements

This work was supported in part by National Key Program (973) for Basic Research (No. 2002CB512805), National Natural Science Foundation of China (No. 30100247), Key Development Project of Science and Technology Committee of Shanghai (CGQ), 100-talent program of Chinese Academy of Sciences (CGQ) and Ho Ying-Dong Education Foundation (CGQ).

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  1. X Cai and Y Yu: Both these authors

Authors and Affiliations

  1. National Key Laboratory for Medicinal Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital, People's Republic of China

    X Cai, Y Yu, L Zhang, P-M Jia, Z Chen, J-H Tong & G-Q Chen

  2. Department of Pathophysiology, Shanghai Second Medical University (SSMU), Shanghai, People's Republic of China

    Y Huang & G-Q Chen

  3. Health Science Center, Shanghai Institutes of Biological Sciences-SSMU, Chinese Academy of Sciences, Shanghai, People's Republic of China

    Q Zhao, W Dai & G-Q Chen

  4. Division of Molecular Carcinogenesis, Department of Medicine, New York Medical College, Valhalla, New York, NY, USA

    W Dai

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Cai, X., Yu, Y., Huang, Y. et al. Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells. Leukemia 17, 1333–1337 (2003). https://doi.org/10.1038/sj.leu.2402983

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