苔抑素，一种来自地衣的次级代谢产物，可降低结直肠癌细胞的干性。

Tumidulin, a Lichen Secondary Metabolite, Decreases the Stemness Potential of Colorectal Cancer Cells.

机构信息

College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea.

Korean Lichen Res. Institute, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea.

出版信息

Molecules. 2018 Nov 14;23(11):2968. doi: 10.3390/molecules23112968.

Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.

地衣产生各种独特的化学物质，这些物质被应用于制药行业。为了筛选能够抑制结直肠癌细胞干性潜能的新型地衣次级代谢产物，我们测试了从智利收集的 11 种地衣样本的丙酮提取物。从中分离得到的 Tumidulin 减少了 CSC221、DLD1 和 HT29 细胞中的球体形成。此外，Tumidulin 处理后，癌症干细胞标志物醛脱氢酶-1（ALDH1）、分化群 133（CD133）、CD44、Lgr5 和 Musashi-1 的 mRNA 表达和蛋白水平降低。Tumidulin 在报告基因检测中降低了神经胶质瘤相关癌基因同源锌指蛋白（Gli）启动子的转录活性，Western blot 验证了 Gli1、Gli2 和 Smoothened（SMO）蛋白水平的降低。此外，Gli 和 SMO 抑制剂的存在阻止了 Tumidulin 的活性。综上所述，这些结果首次证明 Tumidulin 是一种有效的结直肠癌细胞干性抑制剂。