Evidence map›Paper›PMID 39859533›Full record

ArticleInternational journal of molecular sciences2025

Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.

Mikhail G Akimov, Natalia M Gretskaya, Evgenia I Gorbacheva, Nisreen Khadour, Galina D Sherstyanykh, Vladimir V Bezuglov

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Mikhail G AkimovShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.ORCID 0000-0002-7467-4409
Natalia M GretskayaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Evgenia I GorbachevaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.ORCID 0009-0009-3829-8109
Nisreen KhadourShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Galina D SherstyanykhShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Vladimir V BezuglovShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.ORCID 0000-0001-8439-8607

Funding

Russian Scientific Foundation 23-24-00423
6 · The paper itself

Abstract

2-arachnadoyl glycerol (2-AG) is one of the most common endocannabinoid molecules with anti-proliferative, cytotoxic, and pro-proliferative effects on different types of tumors. Typically, it induces cell death via cannabinoid receptor 1/2 (CB1/CB2)-linked ceramide production. In breast cancer, ceramide is counterbalanced by the sphingosine-1-phosphate, and thus the mechanisms of 2-AG influence on proliferation are poorly understood. We evaluated the mechanism of the anti-proliferative action by 2-AG and the influence of lysophaosphatidylinositol (LPI) on it in six human breast cancer cell lines of different tumor degree (MCF-10A, MCF-7, BT-474, BT-20, SK-BR-3, and MDA-MB-231) using resazurin test, inhibitor, blocker, and anti-oxidant analysis, and siRNA interference. To avoid acyl migration in 2-AG, we replaced it with the analog 2-arachidonoyl-1,3-difluoropropanol (2-ADFP) newly synthesized by us. Using a molecular docking approach, we showed that at the CB2 receptor, 2-ADFP and 2-AG were very close to each other. However, 2-ADFP demonstrated a stronger affinity towards CB1 in the antagonist-bound conformation. 2-ADFP was anti-proliferative in all the cell lines tested. The toxicity of 2-ADFP was enhanced by LPI. 2-ADFP activity was reduced or prevented by the CB2 and vanilloid receptor 1 (TRPV1) blockers, inositol triphosphate receptor, CREB, and cyclooxygenase 2 inhibitor, and by anti-oxidant addition. Together with the literature data, these results indicate CB2- and TRPV1-dependent COX-2 induction with concomitant cell death induction by the oxidized molecule's metabolites.

Indexed as

Arachidonic AcidsBreast NeoplasmsEndocannabinoidsGlyceridesLysophospholipidsCell DeathCell Line, TumorCell ProliferationCeramidesCyclooxygenase 2FemaleHumansMolecular Docking SimulationReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2TRPV Cation ChannelsArachidonic AcidsCeramidesCyclooxygenase 2EndocannabinoidsGlyceridesglyceryl 2-arachidonatelysophosphatidylinositolLysophospholipidsReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2TRPV1 protein, humanTRPV Cation Channels2-arachidonoylglycerolbreast cancerCB1CB2COX-2LPITRPV1

Identifiers

PMID39859533
PMCPMC11765598

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.