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AgingHippy
Flwr Pwr



Registered: 04/19/07
Posts: 15,613
Loc: Necropolis
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AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells.
#21684798 - 05/15/15 09:12 PM (8 years, 8 months ago) |
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http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=9000&issue=00000&article=99197&type=abstract
Quote:
Abstract Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist with off-target antitumor activity against pancreatic and colon cancer cells. The current study aimed to characterize the in-vitro antimelanoma activity of AM251. The BRAF V600E mutant melanoma cell line, A375, was used as an in-vitro model system. Characterization tools included a cell viability assay, nuclear morphology assessment, gene expression, western blot, flow cytometry with Annexin V-FITC/7-AAD double staining, cell cycle analyses, and measurements of changes in intracellular cAMP and calcium concentrations. AM251 exerted a marked cytotoxic effect against A375 human melanoma cells with potency comparable with that observed for cisplatin without significant changes in the human dermal fibroblasts viability. AM251, at a concentration that approximates the IC50, downregulated genes encoding antiapoptotic proteins (BCL2 and survivin) and increased transcription levels of proapoptotic BAX, induced alteration of Annexin V reactivity, DNA fragmentation, chromatin condensation in the cell nuclei, and G2/M phase arrest.AM251 also induced a 40% increase in the basal cAMP levels, but it did not affect intracellular calcium concentrations. The involvement of GPR55, TRPA1, and COX-2 in the AM251 mechanism of action was excluded. The combination of AM251 with celecoxib produced a synergistic antitumor activity, although the mechanism underlying this effect remains to be elucidated. This study provides the first evidence of a proapoptotic effect and G2/M cell cycle arrest of AM251 on A375 cells. This compound may be a potential prototype for the development of promising diarylpyrazole derivatives to be evaluated in human cutaneous melanoma.
Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
Sorry if already posted, but found it pretty interesting since someone in my immediate family had melanoma
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Gorlax



Registered: 05/06/08
Posts: 6,695
Last seen: 16 days, 19 hours
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Re: AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. [Re: AgingHippy]
#21685505 - 05/16/15 12:34 AM (8 years, 8 months ago) |
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Interesting. At least something positive has been found about these insane synthetic noids.
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Godfather1376
Psychedelic Aventurer



Registered: 07/07/13
Posts: 1,061
Last seen: 4 years, 1 month
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Re: AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. [Re: Gorlax]
#21685517 - 05/16/15 12:41 AM (8 years, 8 months ago) |
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Wow this might be the first RC to have actual new benefits. They've made RCs for certain drugs as analogues, but other than marijuana, this is in a field pretty much on it's own.
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Connoisseur

Registered: 05/13/11
Posts: 34,686
Last seen: 5 years, 2 months
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Re: AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. [Re: AgingHippy]
#21692532 - 05/17/15 09:54 PM (8 years, 8 months ago) |
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Interesting read, I wonder if other synthnoids or organic cannabinoids would have the same effect.
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