Aims

To study 5-desmethylsinensetin exhibiting potential anticancer activity against breast cancer stem cells and the related molecular mechanism.

Main methods

In this study, isolation of a cancer stem cell (CSC) inhibitor of Artemisia princeps was performed using a silica gel column, a Sephadex gel column, and high-performance liquid chromatography. A single compound was purified via activity-based isolation using mammosphere formation assays. An MTS was used to examine the proliferation of breast cancer cells, and flow cytometry was used to analyze apoptosis and cancer stem cell markers. Western blotting was used to detect the signaling pathway.

Results

The isolated compound was identified as 5-desmethylsinensetin using nuclear magnetic resonance and mass spectrometry. 5-Desmethylsinensetin suppresses the proliferation and mammosphere formation of breast cancer cells, reduces the subpopulations of CD44⁺/CD24^- and ALDH1⁺ cancer cells, and reduces the transcription of the stemness markers Oct4, c-Myc, Nanog and CD44 in Breast CSCs. 5-Desmethylsinensetin inhibits the total and nuclear expression of Stat3 and p-Stat3, as well as the translocation of YAP1. Additionally, 5-desmethylsinensetin reduces the mRNA and protein levels of IL-6.

Conclusion

Our results show that 5-desmethylsinensetin exhibits potential anticancer activity against breast cancer stem cells via Stat3-IL-6 and Stat3-YAP1 signaling.

中文翻译：

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从青蒿中分离出的 5-去甲基芥花素通过 Stat3/IL-6 和 Stat3/YAP1 信号抑制乳腺癌细胞的干性

宗旨

研究对乳腺癌干细胞具有潜在抗癌活性的5-去甲基芥花素及其相关分子机制。

主要方法

在本研究中，使用硅胶柱、Sephadex 凝胶柱和高效液相色谱分离了蒿属的癌症干细胞 (CSC) 抑制剂。使用乳腺球形成试验通过基于活性的分离纯化单一化合物。MTS用于检测乳腺癌细胞的增殖，流式细胞仪用于分析细胞凋亡和癌症干细胞标志物。蛋白质印迹用于检测信号通路。

结果

使用核磁共振和质谱法将分离的化合物鉴定为 5-去甲基芥花素。5-Desmethylsinensetin 抑制乳腺癌细胞的增殖和乳腺球形成，减少 CD44 ⁺ /CD24 ^-和 ALDH1 ⁺癌细胞的亚群，并减少干性标记物 Oct4、c-Myc、Nanog 和 CD44 在乳腺 CSC 中的转录。5-Desmethylsinensetin 抑制 Stat3 和 p-Stat3 的总表达和核表达，以及 YAP1 的易位。此外，5-desmethylsinensetin 降低 IL-6 的 mRNA 和蛋白质水平。

结论

我们的结果表明，5-去甲基芥花素通过 Stat3-IL-6 和 Stat3-YAP1 信号传导对乳腺癌干细胞具有潜在的抗癌活性。