从 Tetrapleura tetraptera (Schumach. & Thonn) Taub.（豆科）中提取的冬凌草甲素和齐墩果酸-3-O-β-D-葡萄糖苷-2'-乙酰胺可诱导人前列腺癌细胞产生强烈的凋亡活性。
Aridanin and oleanane-3- O-β-D-glucoside-2'-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells.
机构信息
Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Research Center for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg-Kingsway Campus, Auckland Park, 2008, South Africa.
Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa; Department of Urology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, D-60596, Frankfurt am Main, Germany; Department of Pharmacotoxicology and Pharmacokinetics, University of Yaounde 1, P.O. Box 1364, Yaounde, Cameroon.
出版信息
J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117298. doi: 10.1016/j.jep.2023.117298. Epub 2023 Oct 20.
ETHNOPHARMACOLOGICAL RELEVANCE
Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines.
MATERIALS AND METHODS
Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed.
RESULTS
Out of the eight (1-8) isolates from T. tetraptera only oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin showed potent cell growth arrest with an estimated CC of 15, 23, 16 and 17, 26, 16 μg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin at 10 μg/mL were noticed. Oleanane-3-O-β-D-glucoside-2'-acetamide and aridanin at 2.5 and 10 μg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin β-1 (10 μg/mL) and integrin β-4 (2.5 μg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8-18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated.
CONCLUSIONS
This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-β-D-glucoside-2'-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.
民族药理学相关性
Tetrapleura tetraptera（Schumach. and Thonn.）Taub.（豆科）是一种热带植物，在喀麦隆药典中用于治疗许多癌症，包括前列腺癌（PCa），这是全球男性死亡的主要原因。本研究的目的是评估 Tetrapleura tetraptera 茎皮提取物中分离得到的化合物对 DU145、PC3 和 LNCaP 癌细胞系的抗癌特性及其潜在机制。
材料和方法
通过硅胶柱层析（CC）从 T. tetraptera 茎皮提取物中分离得到 8 种（1-8）化合物，并通过光谱技术（1D 和 2D NMR、HRESIMS）进行鉴定。通过经过充分验证的 MTT 测定法评估细胞生长情况，而 BrdU 和集落形成测定法提供了细胞增殖指数的信息。此外，通过流式细胞术研究了化合物对细胞周期进程和细胞死亡的影响。测定了细胞黏附、细胞迁移和趋化性以及上皮-间充质转化（EMT）的一些蛋白。
结果
T. tetraptera 中的 8 种（1-8）分离物中，只有齐墩果酸-3-O-β-D-葡萄糖苷-2'-乙酰胺和千里光宁仅在 DU145、PC3 和 LNCaP 细胞上显示出强大的细胞生长抑制作用，估计 CC 为 15、23、16 和 17、26、16μg/mL。在 10μg/mL 时，齐墩果酸-3-O-β-D-葡萄糖苷-2'-乙酰胺和千里光宁诱导 DU145 细胞凋亡增加 15%（DU145）和 25%（LNCaP）。齐墩果酸-3-O-β-D-葡萄糖苷-2'-乙酰胺和千里光宁在 2.5 和 10μg/mL 时降低了 S 期细胞数量，并增加了 G2/M 期细胞数量。在相同浓度下，它们减少了 DU145 细胞的侵袭数量，并在测试浓度下增加了 DU145 细胞与纤连蛋白和胶原蛋白基质的黏附，同时整合素β-1（10μg/mL）和整合素β-4（2.5μg/mL）的表达增加。此外，pcdk1、cdk2、Bcl-2、N-Cad、波形蛋白和细胞角蛋白 8-18 的表达下调，而 p19、p27、p53 pAKT、Bax、caspase-3 和 E-Cad 的表达上调。
结论
本研究首次概述了 Tetrapleura tetraptera 中化合物齐墩果酸-3-O-β-D-葡萄糖苷-2'-乙酰胺（4）和千里光宁（6）的抗癌能力，并提出了它们的潜在作用机制。
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