Cucurbitacin IIa interferes with EGFR-MAPK signaling pathway leads to proliferation inhibition in A549 cells
文献类型： 外文期刊
作者： Zhang, Jie 1 ; Song, Yifan 1 ; Liang, Yuan 1 ; Zou, Haoyang 1 ; Zuo, Peng 2 ; Yan, Mi 1 ; Jing, Siyuan 1 ; Li, Tiezhu 2 ; Wa 1 ;
作者机构： 1.Jilin Univ, Coll Food Sci & Engn, Changchun 130062, Jilin, Peoples R China
2.Jilin Acad Agr Sci, Inst Agr Biotechnol, Changchun 130033, Jilin, Peoples R China
关键词： Epidermal growth factor receptor; Cucurbitacin; Apoptosis; Cell cycle arrest; Molecular simulation
期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：6.023； 五年影响因子：5.844 ）
ISSN： 0278-6915
年卷期： 2019 年 132 卷
页码：
收录情况： SCI
摘要： Cucurbitacin IIa (CuIIa), a tetracyclic triterpenoid harboring anticancer activity, was investigated in A549 cells to reveal its mechanism of targeting on epidermal growth factor receptor (EGFR) signaling pathway. Results showed that CuIIa was capable of inducing apoptosis and cell cycle arrest at G2/M phase. The transcription of EGFR pathway genes and their proteins accumulation was inconsistently influenced by CuIIa. Notably, transcription of Rafl was significantly upregulated, nevertheless, MEK1 and ERK1 were significantly downregulated. On the other hand, the accumulation of the total and phosphorylated proteins of the most members in EGFRmitogen-activated protein kinase (MAPK) pathway, as well as CylclinB1 and survivin were also shifted by CuIIa treatment. Remarkably, total MEK remained constant but survivin completely degraded. Moreover, phosphorylated BRAF continuously increased while Raf1 and MEK decreased continuously. CuIIa was further confirmed to be a tyrosine kinase inhibitor (TKI) of EGFR by kinase inhibition assay. The results of molecular simulation showed that the long side chain of CuIIa occupied the binding pocket of EGFR and the ligand was stabilized at the active site of EGFR. In view of the results above, it is suggested that CuIIa inhibits cell proliferation by interfering the EGFR-MAPK signaling pathway.
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