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The collective nuclear migration of p53 and phosphorylated S473 of Akt during ellipticine-mediated apoptosis in human lung epithelial cancer cells

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An Erratum to this article was published on 16 September 2015

Abstract

Topoisomerase II inhibitor ellipticine effectively suppressed the growth of human non-small-cell-lung-cancer (NSCLC) epithelial cells. Previously, we reported the drug activity was consummated through parallel nucleus migration of p53 and Akt in A549 cells. While inducing cell death, the drug activity was proved related to autophagy through phosphorylated Akt at S473. In addition, ellipticine induced cytotoxicity in p53-null H1299 cells with stable expression of ectopic p53. In this work, we further demonstrated that dominant-negative Akt S473A or p53 shRNA inhibited ellipticine-mediated translocalization of p53 and Akt and attenuated apoptotic cell death in A549 cells. The presence of p53 predates ellipticine-mediated apoptotic cell death, assists in nucleus translocation of phosphorylated Akt and activation of autophagy pathway. Growth inhibition through collaborating p53 and phosphorylated Akt473 in lung epithelial cancer cells provided a new perspective of the topoisomerase inhibitor as an effective cancer therapy agent.

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Acknowledgments

This work was supported in part by the grants from the National Taiwan Normal University, Taipei, Taiwan (103T3040B2).

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  1. Department of Life Science, National Taiwan Normal University, Taipei, Taiwan

    Jing-Ping Wang, Ya-Chu Yu, Shih-Ping Chen, Huan-Chang Liang, Chia-Wei Lin & Kang Fang

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Correspondence to Kang Fang.

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Wang, JP., Yu, YC., Chen, SP. et al. The collective nuclear migration of p53 and phosphorylated S473 of Akt during ellipticine-mediated apoptosis in human lung epithelial cancer cells. Mol Cell Biochem 407, 123–133 (2015). https://doi.org/10.1007/s11010-015-2460-9

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