The Effects and Mechanisms of Sennoside A on Inducing Cytotoxicity, Apoptosis, and Inhibiting Metastasis in Human Chondrosarcoma Cells.
The Effects and Mechanisms of Sennoside A on Inducing Cytotoxicity, Apoptosis, and Inhibiting Metastasis in Human Chondrosarcoma Cells.
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番泻苷A诱导人软骨肉瘤细胞细胞毒、凋亡及抑制转移的作用及机制
DOI：
10.1155/2022/8063497
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发表时间：
2022
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影响因子：
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目前，开发软骨肉瘤（CS）的治疗策略仍然很重要。番泻苷A（Sennoside A，SA）是从番泻叶（Senna）和大黄（Rendezvous）中分离得到的一种二蒽酮糖苷，具有通便、减肥、降血糖等多种生物活性，被广泛用作刺激性泻药、减肥药或膳食补充剂。本研究首次发现SA对CS SW 1353细胞的增殖和转移有抑制作用。SA通过抑制细胞增殖诱导细胞生长停滞。与上皮间质转化（EMT）相关的标志物N-钙粘蛋白和E-钙粘蛋白水平的变化提示SA抑制细胞转移的EMT相关机制。此外，SA还能显著促进CS SW 1353细胞的凋亡，导致细胞死亡。Bax/Bcl 2比值的增加证实了SA对细胞凋亡的线粒体内途径的调节。此外，网络药理学分析预测表明，SA治疗CS的可能途径包括Wnt信号通路。值得注意的是，在CS SW 1353细胞中，SA下调了Wnt途径中组分的蛋白水平，例如Wnt 3a、β-连环蛋白和c-Myc。综上所述，SA抑制CS SW 1353细胞的生长、转移、促进细胞毒性和凋亡可能是通过抑制Wnt/β-catenin通路实现的，提示SA对软骨肉瘤具有潜在的治疗前景。
Currently, developing therapeutic strategies for chondrosarcoma (CS) remains important. Sennoside A (SA), a dianthrone glycoside from Senna and Rhubarb, is widely used as an irritant laxative, weight-loss agent, or dietary supplement, which possesses various bioactive properties such as laxative, antiobesity, and hypoglycemic activities. For the first time, our results suggested that cell proliferation and metastasis were inhibited by SA in CS SW1353 cells. SA induced cell growth arrest by inhibiting cell proliferation. The changes of N-cadherin and E-cadherin levels, the markers associated with epithelial mesenchymal transition (EMT), suggested the EMT-related mechanism of SA in inhibiting cell metastasis. Besides, SA significantly stimulated apoptosis in CS SW1353 cells, leading to cell death. The increase of Bax/Bcl2 ratio confirmed that the internal mitochondrial pathway of apoptosis was regulated by SA. In addition, the prediction of network pharmacology analysis suggested that the possible pathways of SA treatment for CS included the Wnt signaling pathway. Notably, the protein levels of the components in the Wnt pathway, such as Wnt3a, β-catenin, and c-Myc, were downregulated by SA in CS SW1353 cells. To sum up, these results demonstrated that the suppression of the growth, metastasis and the stimulation of cytotoxicity, and apoptosis mediated by SA in CS SW1353 cells were possibly caused by the inhibition of the Wnt/β-catenin pathway, indicating an underlying therapeutic prospect of SA for chondrosarcoma.
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