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Caracasine acid, an ent-3,4-seco-kaurene, promotes apoptosis and cell differentiation through NFkB signal pathway inhibition in leukemia cells.
Martinez, Gricelis Patricia; Mijares, Michael Rodney; Chávez, Katiuska; Suarez, Alirica Isabel; Compagnone, Reinaldo Santi; Chirinos, Perla; De Sanctis, Juan Bautista.
Afiliação
  • Martinez GP; Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • Mijares MR; Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela; Unidad de Biotecnología, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • Chávez K; Unidad de Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • Suarez AI; Unidad de Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • Compagnone RS; Escuela de Química, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • Chirinos P; Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela.
  • De Sanctis JB; Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas, 1050-A, Venezuela; Institute of Molecular and Translational Medicine, Palacky University, Hnevotínská 1333/5, 779 00, Olomouc, Czech Republic. Electronic address: sanctisj@gmail.com.
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 HL60 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-60 cells. CA could be a potential leader compound for the development of new drugs for leukemia treatment in humans.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Leucemia / Diterpenos do Tipo Caurano / Fator de Transcrição RelA / 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
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Leucemia / Diterpenos do Tipo Caurano / Fator de Transcrição RelA / 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