ß-Arrestin inhibition induces autophagy, apoptosis, G0/G1 cell cycle arrest in agonist-activated V2R receptor in breast cancer cells.
Med Oncol
; 38(4): 38, 2021 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-33721131
ABSTRACT
Non-visual arrestins (ß-arrestins) are endocytic proteins that mediate agonist-activated GPCRs internalization and signaling pathways in an independent manner. The involvement of ß-arrestins in cancer invasion and metastasis is increasingly reported. So, it is hypothesized that inhibition of ß-arrestins may diminish the survival chances of cancer cells. This study aimed to evaluate the in vitro impact of inhibiting ß-arrestins on the autophagic and/or apoptotic responsiveness of breast cancer cells. We used Barbadin to selectively inhibit ß-Arr/AP2 interaction in AVP-stimulated V2R receptor of triple-negative breast cancer cells (MDA MB-231). Autophagy was assessed by the microtubule-associated protein 1 light chain 3-II (LC3II), apoptosis was measured by Annexin-V/PI staining and cell cycle distribution was investigated based upon the DNA content using flow cytometry. Barbadin reduced cell viability to 69.1% and increased the autophagy marker LC3II and its autophagic effect disappeared in cells transiently starved in Earle's balanced salt solution (EBSS). Also, Barbadin mildly enhanced the expression of P62 mRNA and arrested 63.7% of cells in G0/G1 phase. In parallel, the drug-induced apoptosis in 29.9% of cells (by AV/PI) and 27.8% of cells were trapped in sub-G1 phase. The apoptotic effect of Barbadin was enhanced when autophagy was inhibited by the PI3K inhibitor (Wortmannin). Conclusively, the data demonstrate the dual autophagic and apoptotic effects of ß-ßArr/AP2 inhibition in triple-negative breast cancer cells. These observations nominate ß-Arrs as selective targets in breast cancer treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_breast_cancer
Assunto principal:
Autofagia
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Receptores de Vasopressinas
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Apoptose
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Pontos de Checagem da Fase G1 do Ciclo Celular
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Beta-Arrestinas
Limite:
Female
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Humans
Idioma:
En
Revista:
Med Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Egito