Inhibition Mechanism of Novel Pyrazolo1,5-apyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 260-265, 2015.
Artículo
en Inglés
| WPRIM
| ID: wpr-242812
ABSTRACT
<p><b>OBJECTIVE</b>To explore the inhibition mechanism and safety of pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives against proliferation of human lung cancer A549 cells, H322 cells, and human umbilical vein endothelial cell (HUVEC).</p><p><b>METHODS</b>Cells were treated with 40 Μmol/L of the ppo3a, ppo3b, ppo3i, and 0.1% DMSO (control) for 48 hours, respectively. Apoptosis was determined by Hoechst 33258 staining assay in H322 and A549 cells. Cell cycle distribution was determined by flow cytometry analysis in A549 cell. LC3-II, p53, and heat shock protein (HSP) 70 protein levels were detected by Western blotting in A549 cells treated with ppo3b for 48 hours. The morphology and viability of HUVEC were observed by inverted microscope and sulforhodamine B (SRB) assay.</p><p><b>RESULTS</b>Ppo3a, ppo3b, and ppo3i significantly induced apoptosis in H322 and A549 cells. A strong G1-phase arrest was concomitant with the growth inhibitory effect on A549 cells. Ppo3b effectively elevated the p53 protein level, but significantly reduced the HSP70 protein level. There were no significantly inhibitory effect on the morphology and viability of HUVEC when treated with ppo3a, ppo3b, and ppo3i.</p><p><b>CONCLUSIONS</b>ppo3a, ppo3b, and ppo3i could inhibit H322 proliferation through apoptosis and inhibit A549 through apoptosis and G1-phase arrest. The protein p53 and HSP70 might involve in the inhibition effects. These derivatives might be a clue to find effective and safe drug for lung cancers.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Farmacología
/
Fisiología
/
Pirazoles
/
Proteína p53 Supresora de Tumor
/
Apoptosis
/
Proteínas HSP70 de Choque Térmico
/
Línea Celular Tumoral
/
Proliferación Celular
/
Puntos de Control del Ciclo Celular
Límite:
Humanos
Idioma:
Inglés
Revista:
Chinese Medical Sciences Journal
Año:
2015
Tipo del documento:
Artículo
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