Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine, Deagu 42472, Republic of Korea.
Magae Bioscience Institute, 49-4 Fujimidai, Tsukuba 300-1263, Japan.
Toxicol In Vitro. 2022 Jun;81:105342. doi: 10.1016/j.tiv.2022.105342. Epub 2022 Mar 4.
4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin, promotes accumulation of HIF-1α. In this study, we investigated the molecular mechanisms of the effect of MAC on cell migration and mesenchymal epithelial transition (EMT) processes in breast cancer cells. MAC upregulated cell motility and migration regardless of cell viability, and promoted EMT features by regulating EMT-related proteins and transcription. In addition, the MAC-induced increase in the EMT was closely related to activation of HIF-1α expression. However, the MAC-induced EMT was not associated with AMPK phosphorylation or intracellular ROS, which stimulate HIF-1α expression. Similarly, HIF-1α-mediated autophagy induced by MAC was not related to EMT-related proteins. Inhibition of HIF-1α activity inhibited MAC-stimulated cell migration and increased MAC-induced cell death, indicating that HIF-1α activation is important for MAC-mediated cell migration and survival in breast cancer cells. Together, these results suggest that MAC can be used to investigate the link between HIF-1α activation and other oncogenes or tumor suppressors in breast cancer cells.
4-O-甲基-ascochlorin (MAC) 是前烯基酚抗生素 ascochlorin 的衍生物，可促进 HIF-1α 的积累。在这项研究中，我们研究了 MAC 对乳腺癌细胞迁移和间充质上皮转化 (EMT) 过程的影响的分子机制。MAC 上调了细胞迁移和迁移，无论细胞活力如何，并且通过调节 EMT 相关蛋白和转录来促进 EMT 特征。此外，MAC 诱导的 EMT 增加与 HIF-1α 表达的激活密切相关。然而，MAC 诱导的 EMT 与刺激 HIF-1α 表达的 AMPK 磷酸化或细胞内 ROS 无关。同样，MAC 诱导的 HIF-1α 介导的自噬与 EMT 相关蛋白无关。抑制 HIF-1α 活性抑制了 MAC 刺激的细胞迁移，并增加了 MAC 诱导的细胞死亡，表明 HIF-1α 的激活对于 MAC 介导的乳腺癌细胞迁移和存活很重要。总之，这些结果表明，MAC 可用于研究 HIF-1α 激活与乳腺癌细胞中其他癌基因或肿瘤抑制因子之间的联系。
