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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
GP. Martinez, MR. Mijares, K. Chávez, AI. Suarez, RS. Compagnone, P. Chirinos, JB. De Sanctis,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
- MeSH
- apoptóza účinky léků MeSH
- buněčná diferenciace účinky léků MeSH
- Croton chemie MeSH
- diterpeny kauranové farmakologie terapeutické užití MeSH
- fytogenní protinádorové látky farmakologie terapeutické užití MeSH
- HL-60 buňky MeSH
- Jurkat buňky MeSH
- leukemie farmakoterapie patologie MeSH
- lidé MeSH
- screeningové testy protinádorových léčiv MeSH
- signální transdukce účinky léků MeSH
- transkripční faktor RelA antagonisté a inhibitory metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
Citace poskytuje Crossref.org
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- $a 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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- $a Mijares, Michael Rodney $u 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.
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