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. 2018 May 9;8:7355. doi: 10.1038/s41598-018-25688-y

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© The Author(s) 2018

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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Scheme of action of the drugs. DMXAA administration to mice bearing tumors leads to the destruction of existing tumor blood vessels. Destruction of the vessels results in the formation of hypoxia areas where HIF-1α transcription factor expression is increased. Activation of HIF-1α triggers several mechanisms that promote tumor growth. Inhibition of HIF-1α after digoxin administration supresses tumor regrowth.