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- 학술저널
- 저자정보
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- 2019.1
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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.
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참고문헌 (40)
참고문헌 신청
Bray F / 2018 / Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries / CA Cancer J Clin 68:394~424
Fulda S / 2010 / Evasion of apoptosis as a cellular stress response in cancer / Int J Cell Biol 2010:370835
Plati J / 2008 / Dysregulation of apoptotic signaling in cancer : molecular mechanisms and therapeutic opportunities / J Cell Biochem 104:1124~1149
Wen C / 2016 / Pseudolaric acid B induces mitotic arrest and apoptosis in both 5-fluorouracil-sensitive and-resistant colorectal cancer cells / Cancer Lett 383:295~308
Wong VK / 2005 / Pseudolaric acid B, a novel microtubule-destabilizing agent that circumvents multidrug resistance phenotype and exhibits antitumor activity in vivo / Clin Cancer Res 11:6002~6011
Fulda S / 2010 / Evasion of apoptosis as a cellular stress response in cancer / Int J Cell Biol 2010:370835
Plati J / 2008 / Dysregulation of apoptotic signaling in cancer : molecular mechanisms and therapeutic opportunities / J Cell Biochem 104:1124~1149
Wen C / 2016 / Pseudolaric acid B induces mitotic arrest and apoptosis in both 5-fluorouracil-sensitive and-resistant colorectal cancer cells / Cancer Lett 383:295~308
Wong VK / 2005 / Pseudolaric acid B, a novel microtubule-destabilizing agent that circumvents multidrug resistance phenotype and exhibits antitumor activity in vivo / Clin Cancer Res 11:6002~6011
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