Antitumor effect of kurarinone and underlying mechanism in small cell lung carcinoma cells.
apoptosis
caspase
invasiveness
kurarinone
migration
small cell lung carcinoma
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2019
2019
Historique:
received:
13
05
2019
accepted:
16
07
2019
entrez:
10
9
2019
pubmed:
10
9
2019
medline:
10
9
2019
Statut:
epublish
Résumé
Kurarinone, a prenylated flavonone isolated from the roots of We investigated the effects of kurarinone on cell proliferation, apoptosis, and migration in H1688 SCLC cells. Cell viability was determined by the MTT assay. Apoptotic indices such as cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptors were evaluated by flow cytometry. Transwell migration and invasion assays were also included. Our results indicated that kurarinone significantly decreased H1688 cell viability and induced the accumulation of sub-G1 fractions by activating caspase-3, -9, and PARP cleavage accompanied by the elevated release of cytochrome c and mitochondrial dysfunction in H1688 cells. Additionally, kurarinone promoted Fas and TRAIL receptor-1 and -2 expression via the caspase-8/Bid pathway, suggesting that kurarinone triggered apoptosis via the mitochondria-mediated and receptor-mediated apoptotic pathways. We also observed that kurarinone repressed migration and invasion capabilities of SCLC cells by suppressing the expression of epithelial-mesenchymal transition-related proteins and matrix metalloproteinases. Our findings provided evidence that kurarinone can induce apoptosis in SCLC cells via multiple mechanisms and delayed the cell migration and invasion of SCLC cells.
Sections du résumé
BACKGROUND
BACKGROUND
Kurarinone, a prenylated flavonone isolated from the roots of
MATERIAL AND METHODS
METHODS
We investigated the effects of kurarinone on cell proliferation, apoptosis, and migration in H1688 SCLC cells. Cell viability was determined by the MTT assay. Apoptotic indices such as cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptors were evaluated by flow cytometry. Transwell migration and invasion assays were also included.
RESULTS
RESULTS
Our results indicated that kurarinone significantly decreased H1688 cell viability and induced the accumulation of sub-G1 fractions by activating caspase-3, -9, and PARP cleavage accompanied by the elevated release of cytochrome c and mitochondrial dysfunction in H1688 cells. Additionally, kurarinone promoted Fas and TRAIL receptor-1 and -2 expression via the caspase-8/Bid pathway, suggesting that kurarinone triggered apoptosis via the mitochondria-mediated and receptor-mediated apoptotic pathways. We also observed that kurarinone repressed migration and invasion capabilities of SCLC cells by suppressing the expression of epithelial-mesenchymal transition-related proteins and matrix metalloproteinases.
CONCLUSION
CONCLUSIONS
Our findings provided evidence that kurarinone can induce apoptosis in SCLC cells via multiple mechanisms and delayed the cell migration and invasion of SCLC cells.
Identifiants
pubmed: 31496721
doi: 10.2147/OTT.S214964
pii: 214964
pmc: PMC6689141
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6119-6131Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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