Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells via the ROSregulated MAPK, STAT3 and NFκB signaling pathways.
Int J Oncol
; 57(2): 550-561, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32626938
ABSTRACT
Isoorientin (ISO) is a naturally occurring Cglycosyl flavone that has various pharmacological properties, such as antibacterial and antiinflammatory effects. However, its underlying molecular mechanisms in human lung cancer cells remain unknown. In the present study, the effects of ISO on the induction of apoptosis and relative molecular mechanisms in A549 human lung cancer cells were investigated. The results of Cell Counting Kit8 assay (CCK8) indicated that ISO exerted significant cytotoxic effects on 3 lung cancer cell lines, but had no obvious sideeffects on normal cells. Moreover, flow cytometry and western blot analysis revealed that ISO induced mitochondrialdependent apoptosis by reducing mitochondrial membrane potential. ISO also increased the expression levels of Bax, cleavedcaspase3 (clecas3) and poly(ADPribose) polymerase (PARP; clePARP), and decreased the expression levels of Bcl2 in A549 cells. Furthermore, ISO induced G2/M cell cycle arrest by decreasing the expression levels of cyclin B1 and CDK1/2, and increasing the expression levels of p21 and p27 in A549 cells. As the duration of ISO treatment increased, intracellular reactive oxygen species (ROS) levels in A549 cells also increased. However, pretreatment of the cells with the ROS scavenger, Nacetylcysteine (NAC), inhibited ISOinduced apoptosis. In addition, ISO increased the expression levels of pp38, pJNK and IκBα; and decreased the expression levels of pextracellular signalregulated kinase (ERK), psignal transducer and activator of transcription (STAT)3, pnuclear factor (NF)κB, NFκB and pIκB; these effects were induced by mitogenactivated protein kinase (MAPK) inhibitors and blocked by NAC. Taken together, the results of the present study indicate that ISO induces the apoptosis of A549 lung cancer cells via the ROSmediated MAPK/STAT3/NFκB signaling pathway, and thus may be a potential drug for use in the treatment of lung cancer.
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Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Sistema de Sinalização das MAP Quinases
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Luteolina
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article