Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press9010.17650/2313-805X-2017-4-1-60-64RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИEffect of acadesine on breast cancer cells under hypoxiaДействие акадезина на клетки рака молочной железы в условиях гипоксииShcherbakovA. M.ЩербаковА. М.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

alex.scherbakov@gmail.comVavilovN. E.ВавиловН. Э.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

AndreevaO. E.АндрееваО. Е.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

TyaglovB. V.ТягловБ. В.
Russian Federation

1 1st Dorozhnyy Proezd, Moscow 117545, Russia

Россия, 117545 Москва, 1-й Дорожный проезд, 1

MironovA. S.МироновА. С.
Russian Federation

1 1st Dorozhnyy Proezd, Moscow 117545, Russia

Россия, 117545 Москва, 1-й Дорожный проезд, 1

ShakulovR. S.ШакуловР. С.
Russian Federation

1 1st Dorozhnyy Proezd, Moscow 117545, Russia

Россия, 117545 Москва, 1-й Дорожный проезд, 1

LobanovK. V.ЛобановК. В.
Russian Federation

1 1st Dorozhnyy Proezd, Moscow 117545, Russia

Россия, 117545 Москва, 1-й Дорожный проезд, 1

YarotskiyS. V.ЯроцкийС. В.
Russian Federation

1 1st Dorozhnyy Proezd, Moscow 117545, Russia

Россия, 117545 Москва, 1-й Дорожный проезд, 1

Shtil’A. A.ШтильА. А.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of RussiaФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава РоссииState Research Institute of Genetics and Selection of Industrial MicroorganismsФГБУ «Государственный научно-исследовательский институт генетики и селекции промышленных микроорганизмов»150120174160641804201718042017Copyright ©; 2017, Shcherbakov A.M., Vavilov N.E., Andreeva O.E., Tyaglov B.V., Mironov A.S., Shakulov R.S., Lobanov K.V., Yarotskiy S.V., Shtil’ A.A.Copyright ©; 2017, Щербаков А.М., Вавилов Н.Э., Андреева О.Е., Тяглов Б.В., Миронов А.С., Шакулов Р.С., Лобанов К.В., Яроцкий С.В., Штиль А.А.2017Shcherbakov A.M., Vavilov N.E., Andreeva O.E., Tyaglov B.V., Mironov A.S., Shakulov R.S., Lobanov K.V., Yarotskiy S.V., Shtil’ A.A.Щербаков А.М., Вавилов Н.Э., Андреева О.Е., Тяглов Б.В., Миронов А.С., Шакулов Р.С., Лобанов К.В., Яроцкий С.В., Штиль А.А.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/90

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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