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GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 октября 2021 г.
- Авторы: Akimov Mikhail G., Gamisonia Alina M., Dudina Polina V., Gretskaya Natalia M., Gaydaryova Anastasia A., Kuznetsov Andrey S., Zinchenko Galina N., Bezuglov Vladimir V.
- Журнал: International Journal of Molecular Sciences
- Том: 22
- Номер: 2
- Год издания: 2021
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 622
- DOI: 10.3390/ijms22020622
- Аннотация: GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca2+, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.
- Добавил в систему: Кузнецов Андрей Сергеевич