Caracasine acid, an ent-3,4-seco-kaurene, promotes apoptosis and cell differentiation through NFkB signal pathway inhibition in leukemia cells.
Eur J Pharmacol
; 862: 172624, 2019 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-31449809
Caracasine acid (CA) is an ent-3,4-seco-kaurene isolated from the plant Croton micans. Decreased cancer cell lines viability was reported upon CA treatment. The present study aimed to investigate the mechanism of CA induced cytotoxicity using two human cell lines, Jurkat E6.1 (human cell T lymphoma) and HL-60 (human acute promyelocytic leukemia). Significant increases of apoptotic cell death markers upon CA treatment were observed: annexin-V positiveness, potential mitochondrial disturbances, cell cycle changes, caspase activation, and CD95 expression. These effects were not detected in normal lymphocytes. CA induced the appearance of Bax, cleaved caspase 3, and cytochrome c release in Jurkat cells, and cleaved caspase 3 and phosphorylated p53 in HL60â¯cells. Likewise, downregulation of anti-apoptotic proteins such as Bcl-x (Jurkat), Bcl-2, and XIAP (HL60) was observed with CA treatment. Both pathways, intrinsic and extrinsic were activated when cell lines were treated with CA. NF-κB p65 inhibition was observed in Jurkat cells and cell differentiation in HL-60â¯cells. CA could be a potential leader compound for the development of new drugs for leukemia treatment in humans.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Leucemia
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Diterpenos do Tipo Caurano
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Fator de Transcrição RelA
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Venezuela
País de publicação:
Holanda