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Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1aстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 16 сентября 2020 г.
- Авторы: Bychkov Maxim, Shulepko Mikhail, Osmakov Dmitry, Andreev Yaroslav, Sudarikova Anastasia, Vasileva Valeria, Pavlyukov Marat S., Latyshev Yaroslav A., Potapov Alexander A., Kirpichnikov Mikhail, Shenkarev Zakhar O., Lyukmanova Ekaterina
- Журнал: Cancers
- Том: 12
- Номер: 7
- Год издания: 2020
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 1
- Последняя страница: 20
- Номер статьи: 1837
- DOI: 10.3390/cancers12071837
- Аннотация: Gliomas are fast growing and highly invasive brain tumors, characterized by tumor microenvironment acidification that drives glioma cell growth and migration. Channels containing Acid-sensing Ion Channel 1a subunit (ASIC1a) mediate amiloride-sensitive cation influx in late stage glioma cells, but not in normal astrocytes. Thus, selective targeting of ASIC1a can be a perspective strategy for glioma treatment. Here, ASIC1a expression in U251 MG and A172 glioma cells, but not in normal astrocytes, was demonstrated. Recombinant analog of mambalgin-2 from black mamba Dendroaspis polylepis inhibited amiloride-sensitive currents at ASIC1a both in Xenopus laevis oocytes and in U251 MG cells, while its mutants with impaired activity towards this channel did not. Mambalgin-2 inhibited U251 MG and A172 glioma cells growth with EC50 in the nanomolar range without affecting the proliferation of normal astrocytes. Notably, mambalgin-2 mutants did not affect glioma cell proliferation, pointing on ASIC1a as the main molecular target of mambalgin-2 in U251 MG and A172 cells. Mambalgin-2 induced a cell cycle arrest, inhibited Cyclin D1 and cyclin-dependent kinases (CDK) phosphorylation and caused apoptosis in U251 MG and A172 cells. Moreover, mambalgin-2 inhibited the growth of low-passage primary cells from a patient with glioblastoma. Altogether, our data point to mambalgin-2 as a useful hit for the development of new drugs for glioma treatment.
- Добавил в систему: Люкманова Екатерина Назымовна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Иллюстрация | Latyishev_Potapov_cancers-12-01837-s001.pdf | 868,9 КБ | 15 сентября 2020 [Pronkina_TE_nsi] |