白头草原提取物对软骨肉瘤细胞转移的抑制作用。
Inhibitory effects on chondrosarcoma cell metastasis by Senna alata extract.
机构信息
Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, 114 Sukhumvit 23, Bangkok 10110, Thailand.
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, 114 Sukhumvit 23, Bangkok 10110, Thailand.
出版信息
Biomed Pharmacother. 2021 May;137:111337. doi: 10.1016/j.biopha.2021.111337. Epub 2021 Feb 12.
BACKGROUND
Senna alata L. Roxb or candle bush is a traditional medicinal plant with a wide range of biological activities including anti-inflammatory, antimicrobial and antifungal. Leaf extract of S. alata showed the anti-tumor activity in various cancer cell lines. In this study, we focused on the inhibitory mechanism of S. alata extract (SAE) on cancer metastasis including cell migration, cell invasion and signaling pathways in chondrosarcoma SW1353 cells.
PURPOSE
This study aimed to evaluate the anti-metastatic mechanisms of Senna alata extract on chondrosarcoma SW1353 cells.
METHODS
Screening for phytochemicals in biologically active fraction of SAE was analysed by H NMR spectroscopy. Cell viability and cytoxicity were determined by using MTT assay. Cell migration was observed by scratch wound healing and transwell migration assay. Cell invasion and cell adhesion assay were examined by Matrigel coated transwell chambers or plates. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), MAPKs and PI3K/Akt signaling pathways and NF-κB were detected by Western blot analysis.
RESULTS
The SAE treatment at the sub-cytoxic and non-cytotoxic concentrations significantly inhibited cell migration, cell invasion and cell adhesion of SW1353 cells in a dose-dependent manner. The results from Western blot analysis showed decreased MMP-2 and MMP-9 expression, while increased TIMP-1 and TIMP-2 expression in SAE treated cells. Moreover, SAE suppressed phosphorylation of ERK1/2, p38 and Akt but decreased NF-κB transcription factor expression in SW1353 cells.
CONCLUSION
These results revealed that SAE could reduce MMP-2 and MMP-9 expression by downregulation of NF-κB which is downstream of MAPKs and PI3K/Akt signaling pathway in SW1353 cells resulting in reduced cancer cell migration and invasion. Therefore, SAE may have the potential use as an alternative treatment of chondrosarcoma metastasis.
背景
番泻叶（ Senna alata L. Roxb ）是一种传统药用植物，具有广泛的生物活性，包括抗炎、抗菌和抗真菌作用。番泻叶的叶提取物在各种癌细胞系中显示出抗肿瘤活性。在这项研究中，我们专注于番泻叶提取物（ SAE ）对软骨肉瘤 SW1353 细胞转移的抑制机制，包括细胞迁移、细胞侵袭和信号通路。
目的
本研究旨在评估番泻叶提取物对软骨肉瘤 SW1353 细胞的抗转移机制。
方法
采用 H NMR 光谱分析生物活性部位 SAE 的植物化学成分筛选。采用 MTT 法测定细胞活力和细胞毒性。通过划痕愈合和 Transwell 迁移实验观察细胞迁移。通过 Matrigel 包被 Transwell 室或板检测细胞侵袭和细胞黏附实验。通过 Western blot 分析检测基质金属蛋白酶（ MMPs ）和金属蛋白酶组织抑制剂（ TIMPs ）、MAPKs 和 PI3K/Akt 信号通路和 NF-κB 的表达。
结果
亚细胞毒性和非细胞毒性浓度的 SAE 处理显著抑制了 SW1353 细胞的迁移、侵袭和黏附，呈剂量依赖性。Western blot 分析结果显示，SAE 处理的细胞中 MMP-2 和 MMP-9 的表达降低，而 TIMP-1 和 TIMP-2 的表达增加。此外，SAE 抑制了 ERK1/2 、 p38 和 Akt 的磷酸化，但降低了 SW1353 细胞中 NF-κB 转录因子的表达。
结论
这些结果表明，SAE 可通过下调 NF-κB 减少 MMP-2 和 MMP-9 的表达，NF-κB 是 MAPKs 和 PI3K/Akt 信号通路的下游靶点，从而减少 SW1353 细胞的迁移和侵袭。因此，SAE 可能具有作为软骨肉瘤转移的替代治疗方法的潜力。
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