Apoptosis induced by bruceine D in human nonsmallcell lung cancer cells involves mitochondrial ROSmediated death signaling.
Int J Mol Med
; 44(6): 2015-2026, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31638181
ABSTRACT
Bruceine D is one of the active components of Brucea javanica (L.) Merr., which is widely used to treat cancer in China. The aim of the present study was to evaluate the potential effect of bruceine D against nonsmallcell lung cancer (NSCLC) cells and delineate its underlying mechanisms. The results indicated that treatment with bruceine D markedly inhibited the proliferation of wildtype NSCLC cells and epidermal growth factor receptormutant cells in a dose and timedependent manner, and significantly decreased the colonyforming ability and migration of A549 cells. Hoechst 33342 staining and flow cytometric analysis demonstrated that treatment with bruceine D effectively induced apoptosis of A549 cells. In addition, the proapoptotic effect of bruceine D was found to be associated with G0G1 cell cycle arrest, accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde, depletion of glutathione levels and disruption of mitochondrial membrane potential. Additionally, pretreatment with Nacetylcysteine, a ROS scavenger, significantly attenuated the bruceine Dinduced inhibition in A549 cells. Western blotting demonstrated that treatment with bruceine D significantly suppressed the expression of the antiapoptotic proteins Bcl2, BclxL and Xlinked inhibitor of apoptosis, enhanced the expression levels of apoptotic proteins Bax and Bak, and inhibited the expression of procaspase3 and procaspase8. Based on these results, it may be suggested that inhibition of A549 NSCLC cell proliferation by bruceine D is associated with the modulation of ROSmitochondrialmediated death signaling. This novel insight may provide further evidence to verify the anticancer efficacy of B. javanica, and support a role for bruceine D in the antiNSCLC treatment.
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Base de datos:
MEDLINE
Asunto principal:
Especies Reactivas de Oxígeno
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Carcinoma de Pulmón de Células no Pequeñas
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Cuassinas
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Proliferación Celular
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article