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Formosanin C suppresses cancer cell proliferation and migration by impeding autophagy machinery
The Kaohsiung Journal of Medical Sciences ( IF 3.3 ) Pub Date : 2023-03-03 , DOI: 10.1002/kjm2.12658
Man-Ling Chu, Pei-Wen Lin, Yu-Wen Liu, Shan-Ying Wu, Sheng-Hui Lan, Chun-Li Su, Hsiao-Sheng Liu

Formosanin C (FC) is a natural compound extracted from Paris formosana Hayata with anticancer activity. FC induces both autophagy and apoptosis in human lung cancer cells. FC-induced depolarization of mitochondrial membrane potential (MMP) may trigger mitophagy. In this study, we clarified the effect of FC on autophagy, mitophagy, and the role of autophagy in FC-related cell death and motility. We found FC caused the continuous increase of LC3 II (representing autophagosomes) from 24 to 72 h without degradation after treatment of lung and colon cancer cells, indicating that FC blocks autophagic progression. In addition, we confirmed that FC also induces early stage autophagic activity. Altogether, FC is not only an inducer but also a blocker of autophagy progression. Moreover, FC increased MMP accompanied by overexpression of COX IV (mitochondria marker) and phosphorylated Parkin (p-Parkin, mitophagy marker) in lung cancer cells, but no colocalization of LC3 with COX IV or p-Parkin was detected under confocal microscopy. Moreover, FC could not block CCCP (mitophagy inducer)-induced mitophagy. These results imply that FC disrupts mitochondria dynamics in the treated cells, and the underlying mechanism deserves further exploration. Functional analysis reveals that FC suppresses cell proliferation and motility through apoptosis and EMT-related pathway, respectively. In conclusion, FC acts as an inducer as well as a blocker of autophagy that results in cancer cell apoptosis and decreased motility. Our findings shed the light on the development of combined therapy with FC and clinical anticancer drugs for cancer treatment.

中文翻译:

Formosin C 通过阻碍自噬机制抑制癌细胞增殖和迁移

Formosanin C (FC) 是从重楼中提取的天然化合物具有抗癌活性的早田。FC 在人肺癌细胞中诱导自噬和细胞凋亡。FC 诱导的线粒体膜电位 (MMP) 去极化可能引发线粒体自噬。在这项研究中,我们阐明了 FC 对自噬、线粒体自噬的影响,以及自噬在 FC 相关细胞死亡和运动中的作用。我们发现 FC 导致 LC3 II(代表自噬体)在处理肺癌和结肠癌细胞后从 24 小时持续增加到 72 小时而没有降解,表明 FC 阻断了自噬进程。此外,我们证实 FC 还诱导早期自噬活性。总而言之,FC 不仅是诱导剂,还是自噬进程的阻断剂。此外,FC 增加了 MMP,伴随着 COX IV(线粒体标记物)和磷酸化帕金蛋白(p-Parkin,mitophagy 标记)在肺癌细胞中,但在共聚焦显微镜下未检测到 LC3 与 COX IV 或 p-Parkin 的共定位。此外,FC 不能阻断 CCCP(线粒体自噬诱导剂)诱导的线粒体自噬。这些结果意味着 FC 破坏了处理细胞中的线粒体动力学,其潜在机制值得进一步探索。功能分析表明,FC 分别通过细胞凋亡和 EMT 相关途径抑制细胞增殖和运动。总之,FC 充当诱导剂以及自噬阻断剂,导致癌细胞凋亡和运动性降低。我们的研究结果揭示了 FC 和临床抗癌药物联合治疗癌症治疗的发展。FC 不能阻断 CCCP(线粒体自噬诱导剂)诱导的线粒体自噬。这些结果意味着 FC 破坏了处理细胞中的线粒体动力学,其潜在机制值得进一步探索。功能分析表明,FC 分别通过细胞凋亡和 EMT 相关途径抑制细胞增殖和运动。总之,FC 充当诱导剂以及自噬阻断剂,导致癌细胞凋亡和运动性降低。我们的研究结果揭示了 FC 和临床抗癌药物联合治疗癌症治疗的发展。FC 不能阻断 CCCP(线粒体自噬诱导剂)诱导的线粒体自噬。这些结果意味着 FC 破坏了处理细胞中的线粒体动力学,其潜在机制值得进一步探索。功能分析表明,FC 分别通过细胞凋亡和 EMT 相关途径抑制细胞增殖和运动。总之,FC 充当诱导剂以及自噬阻断剂,导致癌细胞凋亡和运动性降低。我们的研究结果揭示了 FC 和临床抗癌药物联合治疗癌症治疗的发展。功能分析表明,FC 分别通过细胞凋亡和 EMT 相关途径抑制细胞增殖和运动。总之,FC 充当诱导剂以及自噬阻断剂,导致癌细胞凋亡和运动性降低。我们的研究结果揭示了 FC 和临床抗癌药物联合治疗癌症治疗的发展。功能分析表明,FC 分别通过细胞凋亡和 EMT 相关途径抑制细胞增殖和运动。总之,FC 充当诱导剂以及自噬阻断剂,导致癌细胞凋亡和运动性降低。我们的研究结果揭示了 FC 和临床抗癌药物联合治疗癌症治疗的发展。
更新日期:2023-03-03
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