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2-Oxonanonoidal Antibiotic Actinolactomycin Inhibits Cancer Progression by Suppressing HIF-1α

1
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
2
Guangzhou First People’s Hospital, School of Medicine and Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China
3
Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(5), 439; https://doi.org/10.3390/cells8050439
Received: 23 March 2019 / Revised: 27 April 2019 / Accepted: 2 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Gene Regulation by HIFs during Hypoxia)
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Abstract

HIF-1 serves as an important regulator in cell response to hypoxia. Due to its key role in promoting tumor survival and progression under hypoxia, HIF-1 has become a promising target of cancer therapy. Thus far, several HIF-1 inhibitors have been identified, most of which are from synthesized chemical compounds. Here, we report that ALM (ActinoLactoMycin), a compound extracted from metabolites of Streptomyces flavoretus, exhibits inhibitory effect on HIF-1α. Mechanistically, we found that ALM inhibited the translation of HIF-1α protein by suppressing mTOR signaling activity. Treatment with ALM induced cell apoptosis and growth inhibition of cancer cells both in vitro and in vivo in a HIF-1 dependent manner. More interestingly, low dose of ALM treatment enhanced the anti-tumor effect of Everolimus, an inhibitor of mTOR, suggesting its potential use in combination therapy of tumors, especially solid tumor patients. Thus, we identified a novel HIF-1α inhibitor from the metabolites of Streptomyces flavoretus, which shows promising anti-cancer potential. View Full-Text
Keywords: ALM; hypoxia; HIF-1α; inhibitor; mTOR; combination therapy ALM; hypoxia; HIF-1α; inhibitor; mTOR; combination therapy
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Cheng, J.; Hu, L.; Yang, Z.; Suo, C.; Wang, Y.J.; Gao, P.; Cui, C.; Sun, L. 2-Oxonanonoidal Antibiotic Actinolactomycin Inhibits Cancer Progression by Suppressing HIF-1α. Cells 2019, 8, 439.

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