Caracasine acid, an ent-3,4-seco-kaurene, promotes apoptosis and cell differentiation through NFkB signal pathway inhibition in leukemia cells
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
31449809
DOI
10.1016/j.ejphar.2019.172624
PII: S0014-2999(19)30576-X
Knihovny.cz E-resources
- Keywords
- Annexin-V, Apoptosis, Cancer, Caracasine acid, Croton, Kaurene compounds, Leukemia, NF-κB,
- MeSH
- Apoptosis drug effects MeSH
- Cell Differentiation drug effects MeSH
- Croton chemistry MeSH
- Diterpenes, Kaurane pharmacology therapeutic use MeSH
- Antineoplastic Agents, Phytogenic pharmacology therapeutic use MeSH
- HL-60 Cells MeSH
- Jurkat Cells MeSH
- Leukemia drug therapy pathology MeSH
- Humans MeSH
- Drug Screening Assays, Antitumor MeSH
- Signal Transduction drug effects MeSH
- Transcription Factor RelA antagonists & inhibitors metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- caracasine acid MeSH Browser
- Diterpenes, Kaurane MeSH
- Antineoplastic Agents, Phytogenic MeSH
- Rela protein, mouse MeSH Browser
- Transcription Factor 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.
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