Email this article Effect of acadesine on breast cancer cells under hypoxia
- Authors: Shcherbakov A.M.1, Vavilov N.E.1, Andreeva O.E.1, Tyaglov B.V.2, Mironov A.S.2, Shakulov R.S.2, Lobanov K.V.2, Yarotskiy S.V.2, Shtil’ A.A.1
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Affiliations:
- N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
- State Research Institute of Genetics and Selection of Industrial Microorganisms
- Issue: Vol 4, No 1 (2017)
- Pages: 60-64
- Section: RESEARCH ARTICLES
- Published: 18.04.2017
- URL: https://umo.abvpress.ru/jour/article/view/90
- DOI: https://doi.org/10.17650/2313-805X-2017-4-1-60-64
- ID: 90
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Abstract
The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК), an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen), acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia), acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha) transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.
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About the authors
A. M. Shcherbakov
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Author for correspondence.
Email: alex.scherbakov@gmail.com
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
N. E. Vavilov
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
O. E. Andreeva
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
B. V. Tyaglov
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: fake@neicon.ru
1 1st Dorozhnyy Proezd, Moscow 117545, Russia Russian Federation
A. S. Mironov
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: fake@neicon.ru
1 1st Dorozhnyy Proezd, Moscow 117545, Russia Russian Federation
R. S. Shakulov
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: fake@neicon.ru
1 1st Dorozhnyy Proezd, Moscow 117545, Russia Russian Federation
K. V. Lobanov
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: fake@neicon.ru
1 1st Dorozhnyy Proezd, Moscow 117545, Russia Russian Federation
S. V. Yarotskiy
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: fake@neicon.ru
1 1st Dorozhnyy Proezd, Moscow 117545, Russia Russian Federation
A. A. Shtil’
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
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