Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells.
J Cell Biochem
; 120(4): 5628-5635, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30317654
ABSTRACT
BACKGROUND:
There is still no clinically approved agent for mutant KRAS, which is the most common alteration in non-small-cell lung cancer (NSCLC). Flavopiridol is a semisynthetic flavonoid that inhibits cell growth through cyclin-dependent kinases in G1/S or G2/M of the cell cycle and induces apoptosis. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549, Calu-1, and H2009 cell lines.METHODS:
The cytotoxic effects of flavopiridol on NSCLC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability test. The cells were treated with 200 and 400 nM flavopiridol, and, then, apoptosis, survival, and metastasis-related protein expressions were determined by Western blot analysis. The antimetastatic effects of flavopiridol were assessed by wound healing and Galectin-3 activity assay.RESULTS:
Flavopiridol drastically affected toxicity in all KRAS mutant NSCLC cells at nanomolar concentrations. Also, it could efficiently inhibit wound healing and Galectin-3 activity in all the cells tested. However, the metastasis-related protein expressions did not reflect these obvious effects on blotting. p-Erk was activated as a cellular survival mechanism to escape apoptosis in all the cells tested.CONCLUSION:
Although there are many mechanisms that still need to be elucidated, flavopiridol can be used as a metastasis inhibitor and an apoptosis inducer in KRAS mutant NSCLC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
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Flavonoides
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Proteínas Proto-Oncogênicas p21(ras)
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Carcinoma Pulmonar de Células não Pequenas
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
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Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article