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Polygonatum odoratum lectin induces apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK pathway in human MCF-7 breast cancer cells

机译:玉竹凝集素通过靶向人MCF-7乳腺癌细胞中EGFR介导的Ras-Raf-MEK-ERK途径诱导凋亡和自噬

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摘要

Polygonatum odoratum lectin (POL), a mannose-binding GNA-related lectin, has been reported to display remarkable anti-proliferative and apoptosis-inducing activities toward a variety of cancer cells; however, the precise molecular mechanisms by which POL induces cancer cell death are still elusive. In the current study, we found that POL could induce both apoptosis and autophagy in human MCF-7 breast cancer cells. Subsequently, we found that POL induced MCF-7 cell apoptosis via the mitochondrial pathway. Additionally, we also found that POL induces MCF-7 cell apoptosis via EGFR-mediated Ras-Raf-MEK-ERK pathway, suggesting that POL may be a potential EGFR inhibitor. Finally, we used proteomics analyses for exploring more possible POL-induced pathways with EGFR, Ras, Raf, MEK and ERK, some of which were consistent with our in silico network prediction. Taken together, these results demonstrate that POL induces MCF-7 cell apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK signaling pathway, which would provide a new clue for exploiting POL as a potential anti-neoplastic drug for future cancer therapy.
机译:据报道,一种与甘露糖结合的GNA相关凝集素-玉竹凝集素(POL)对多种癌细胞具有显着的抗增殖和凋亡诱导活性。但是,POL诱导癌细胞死亡的确切分子机制仍然难以捉摸。在当前的研究中,我们发现POL可以诱导人MCF-7乳腺癌细胞凋亡和自噬。随后,我们发现POL通过线粒体途径诱导MCF-7细胞凋亡。此外,我们还发现POL通过EGFR介导的Ras-Raf-MEK-ERK途径诱导MCF-7细胞凋亡,提示POL可能是潜在的EGFR抑制剂。最后,我们使用蛋白质组学分析来探索更多可能的EGFR诱导的EGFR,Ras,Raf,MEK和ERK途径,其中一些与我们的计算机网络预测相符。综上所述,这些结果表明POL通过靶向EGFR介导的Ras-Raf-MEK-ERK信号传导途径诱导MCF-7细胞凋亡和自噬,这将为利用POL作为未来癌症的潜在抗肿瘤药物提供新的线索。治疗。

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