Pseudolaric acid B inhibits PAX2 expression through Wnt signaling and induces BAX expression, therefore promoting apoptosis in HeLa cervical cancer cells / 부인종양
Journal of Gynecologic Oncology
; : e77-2019.
Article
Dans En
| WPRIM
| ID: wpr-764546
Responsable en Bibliothèque :
WPRO
ABSTRACT
OBJECTIVES:
Pseudolaric acid B (PAB) has been shown to inhibit the growth of various tumor cells, but the molecular details of its function are still unknown. This study investigated the molecular mechanisms by which PAB induces apoptosis in HeLa cells.METHODS:
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to investigate the effect of PAB treatment in various cervical cancer cell lines. Annexin V/propidium iodide staining combined with flow cytometry and Hoechst 33258 staining were used to assess PAB-induced apoptosis. Additionally, we performed bioinformatics analyses and identified a paired box 2 (PAX2) binding site on the BAX promoter. We then validated the binding using luciferase and chromatin immunoprecipitation assays. Finally, western blotting assays were used to investigate PAB effect on the Wnt signaling and the involved signaling molecules.RESULTS:
PAB promotes apoptosis and downregulates PAX2 expression in HeLa cells in a time- and concentration-dependent manner. PAX2 binds to the promoter of BAX and inhibits its expression; therefore, PAX2 inhibition is associated with increased levels of BAX, which induces apoptosis of HeLa cells via the mitochondrial pathway. Additionally, PAB inhibits classical Wnt signaling.CONCLUSION:
PAB effectively inhibits Wnt signaling and PAX2 expression, and increases BAX levels, which induce apoptosis in HeLa cells. Therefore, PAB is a promising natural molecule for the treatment of cervical cancer.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Sites de fixation
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Cellules HeLa
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Lignée cellulaire
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Tumeurs du col de l'utérus
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Technique de Western
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Apoptose
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Biologie informatique
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Immunoprécipitation de la chromatine
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Voie de signalisation Wnt
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Cytométrie en flux
Limites du sujet:
Humans
langue:
En
Texte intégral:
Journal of Gynecologic Oncology
Année:
2019
Type:
Article