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. 2017 Aug 30;7:9989. doi: 10.1038/s41598-017-10577-7

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Signaling pathways altered by XWL-1-48. XWL-1-48 is a novel orally topoisomerase II inhibitor and exerts potent in vitro and in vivo antitumor activity against HCC. Treatment of XWL-1-48 significantly inhibited topoisomerase II activity, activated ATM/Chk2/Cdc25A and ATM/p53/p21 pathways, triggered DNA damage response, arrested cell cycle at S phase, and induced mitochondria- and death receptor-mediated apoptosis. Meanwhile, XWL-1-48 strongly blocked PI3K/Akt/Mdm2 pathway, enhanced degradation of Mdm2, and suppressed HCC cell survival.