College of Life Science, Yangtze University, Jingzhou, China.
College of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan, China.
J Food Biochem. 2022 Oct;46(10):e14374. doi: 10.1111/jfbc.14374. Epub 2022 Aug 20.
Condensed tannins the polyphenolic compounds that are widespread in plants have been proved to have antitumor potential. Here, we purified the bioactive condensed tannins from leaves of Ulmus pumila L. and explored their structural characteristics, antitumor effect on TFK-1 cholangiocarcinoma cells as well as the related potential mechanism. The UV-Vis, FT-IR spectroscopy, ESI-Full-MS, and thiolysis-HPLC-ESI-MS demonstrated that U. pumila condensed tannins (UCTs) consisted essentially of procyanidins with epicatechin as the main flavan-3-ol extension unit. The UCTs could significantly reduce the survival rate of human cholangiocarcinoma TFK-1, SK-CHA-1, and MZ-CHA-1 cells with the better inhibitory effect on TFK-1 cell proliferation. Flow cytometric assay showed that UCTs affected TFK-1 survival by G2/M phase arrest and inducing apoptosis in a dose-dependent manner. In addition, a total of 6592 differentially expressed genes (DEGs), consisting of 94 upregulated and 6498 downregulated DEGs, were identified between untreated and UCTs-treated TFK-1 cells using RNA-seq technology. Enrichment analysis based on the KEGG database revealed that these DEGs were closely associated with cell cycle and p53 apoptotic signaling pathways. Furthermore, qRT-PCR confirmed that treatment of UCTs to TFK-1 cells caused significant changes in the expression of cyclin E, cdc25 A, cytochrome c, caspase-3, and caspase-8. These results indicated that UCTs exhibited the growth inhibition effect on TFK-1 cells possibly via G2/M cell cycle arrest and activation of caspase-cascade to induce apoptosis, and had potential as an anti-cholangiocarcinoma drug for further development. PRACTICAL APPLICATIONS: Ulmus pumila L. as a valuable tree species has been widely used in fields of medicine and food. Condensed tannins, the polyphenolic compounds widespread in plants, have been proved to have antitumor potential and be safe to normal cells. In this study, the condensed tannins from leaves of U. pumila (UCTs) remarkably suppressed cholangiocarcinoma (CCA) cell viability possibly via G2/M cell cycle arrest and activation of caspase-cascade to induce apoptosis. The results provided evidence for the application of UCTs as a potential therapeutic drug for CCA tumor.
单宁是一种广泛存在于植物中的多酚化合物，已被证明具有抗肿瘤潜力。在这里，我们从榆树叶片中纯化了具有生物活性的缩合单宁，并研究了它们的结构特征、对 TFK-1 胆管癌细胞的抗肿瘤作用以及相关的潜在机制。紫外可见分光光度法、傅里叶变换红外光谱法、电喷雾全质谱法和硫解高效液相色谱-电喷雾质谱法表明，榆树缩合单宁（UCTs）主要由表儿茶素作为主要黄烷-3-醇扩展单元的原花青素组成。UCTs 能显著降低人胆管癌细胞 TFK-1、SK-CHA-1 和 MZ-CHA-1 的存活率，对 TFK-1 细胞增殖的抑制作用更好。流式细胞术检测结果表明，UCTs 通过 G2/M 期阻滞和剂量依赖性诱导细胞凋亡影响 TFK-1 的存活。此外，使用 RNA-seq 技术在未处理和 UCTs 处理的 TFK-1 细胞之间共鉴定出 6592 个差异表达基因（DEGs），其中包括 94 个上调和 6498 个下调的 DEGs。基于 KEGG 数据库的富集分析表明，这些 DEGs 与细胞周期和 p53 凋亡信号通路密切相关。此外，qRT-PCR 证实 UCTs 处理 TFK-1 细胞导致细胞周期蛋白 E、cdc25A、细胞色素 c、caspase-3 和 caspase-8 的表达发生显著变化。这些结果表明，UCTs 对 TFK-1 细胞的生长抑制作用可能是通过 G2/M 细胞周期阻滞和激活 caspase 级联诱导细胞凋亡来实现的，并且具有作为进一步开发的抗胆管癌药物的潜力。实际应用：榆树作为一种有价值的树种，已广泛应用于医学和食品领域。缩合单宁是一种广泛存在于植物中的多酚化合物，已被证明具有抗肿瘤潜力，对正常细胞是安全的。在这项研究中，从榆树叶片中分离得到的缩合单宁（UCTs）显著抑制胆管癌（CCA）细胞活力，可能是通过 G2/M 细胞周期阻滞和激活 caspase 级联诱导细胞凋亡。结果为 UCTs 作为潜在的 CCA 肿瘤治疗药物的应用提供了证据。
