Caracasine acid, an ent-3,4-seco-kaurene, promotes apoptosis and cell differentiation through NFkB signal pathway inhibition in leukemia cells
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
31449809
DOI
10.1016/j.ejphar.2019.172624
PII: S0014-2999(19)30576-X
Knihovny.cz E-zdroje
- Klíčová slova
- Annexin-V, Apoptosis, Cancer, Caracasine acid, Croton, Kaurene compounds, Leukemia, NF-κB,
- 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
- Názvy látek
- caracasine acid MeSH Prohlížeč
- diterpeny kauranové MeSH
- fytogenní protinádorové látky MeSH
- Rela protein, mouse MeSH Prohlížeč
- transkripční faktor RelA 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
