Effect of acadesine on breast cancer cells under hypoxia
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 energ...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
ABV-press
2017-04-01
|
| Series: | Успехи молекулярной онкологии |
| Subjects: | |
| Online Access: | https://umo.abvpress.ru/jour/article/view/90 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849241238750887936 |
|---|---|
| author | A. M. Shcherbakov N. E. Vavilov O. E. Andreeva B. V. Tyaglov A. S. Mironov R. S. Shakulov K. V. Lobanov S. V. Yarotskiy A. A. Shtil’ |
| author_facet | A. M. Shcherbakov N. E. Vavilov O. E. Andreeva B. V. Tyaglov A. S. Mironov R. S. Shakulov K. V. Lobanov S. V. Yarotskiy A. A. Shtil’ |
| author_sort | A. M. Shcherbakov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-27b9b4ec2bbf405bbd22e403365316d7 |
| institution | Kabale University |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| publishDate | 2017-04-01 |
| publisher | ABV-press |
| record_format | Article |
| series | Успехи молекулярной онкологии |
| spelling | doaj-art-27b9b4ec2bbf405bbd22e403365316d72025-08-20T04:00:14ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872017-04-0141606410.17650/2313-805X-2017-4-1-60-6486Effect of acadesine on breast cancer cells under hypoxiaA. M. Shcherbakov0N. E. Vavilov1O. E. Andreeva2B. V. Tyaglov3A. S. Mironov4R. S. Shakulov5K. V. Lobanov6S. V. Yarotskiy7A. A. Shtil’8N.N. Blokhin Russian Cancer Research Center, Ministry of Health of RussiaN.N. Blokhin Russian Cancer Research Center, Ministry of Health of RussiaN.N. Blokhin Russian Cancer Research Center, Ministry of Health of RussiaState Research Institute of Genetics and Selection of Industrial MicroorganismsState Research Institute of Genetics and Selection of Industrial MicroorganismsState Research Institute of Genetics and Selection of Industrial MicroorganismsState Research Institute of Genetics and Selection of Industrial MicroorganismsState Research Institute of Genetics and Selection of Industrial MicroorganismsN.N. Blokhin Russian Cancer Research Center, Ministry of Health of RussiaThe 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.https://umo.abvpress.ru/jour/article/view/90acadesinebreast cancermcf-7 cell linehypoxiatranscription factors |
| spellingShingle | A. M. Shcherbakov N. E. Vavilov O. E. Andreeva B. V. Tyaglov A. S. Mironov R. S. Shakulov K. V. Lobanov S. V. Yarotskiy A. A. Shtil’ Effect of acadesine on breast cancer cells under hypoxia Успехи молекулярной онкологии acadesine breast cancer mcf-7 cell line hypoxia transcription factors |
| title | Effect of acadesine on breast cancer cells under hypoxia |
| title_full | Effect of acadesine on breast cancer cells under hypoxia |
| title_fullStr | Effect of acadesine on breast cancer cells under hypoxia |
| title_full_unstemmed | Effect of acadesine on breast cancer cells under hypoxia |
| title_short | Effect of acadesine on breast cancer cells under hypoxia |
| title_sort | effect of acadesine on breast cancer cells under hypoxia |
| topic | acadesine breast cancer mcf-7 cell line hypoxia transcription factors |
| url | https://umo.abvpress.ru/jour/article/view/90 |
| work_keys_str_mv | AT amshcherbakov effectofacadesineonbreastcancercellsunderhypoxia AT nevavilov effectofacadesineonbreastcancercellsunderhypoxia AT oeandreeva effectofacadesineonbreastcancercellsunderhypoxia AT bvtyaglov effectofacadesineonbreastcancercellsunderhypoxia AT asmironov effectofacadesineonbreastcancercellsunderhypoxia AT rsshakulov effectofacadesineonbreastcancercellsunderhypoxia AT kvlobanov effectofacadesineonbreastcancercellsunderhypoxia AT svyarotskiy effectofacadesineonbreastcancercellsunderhypoxia AT aashtil effectofacadesineonbreastcancercellsunderhypoxia |