Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University , Shenyang 110819, People's Republic of China.
Laboratory of Metabolic Disease Research and Drug Development, China Medical University , Shenyang 110001, People's Republic of China.
J Nat Prod. 2017 Apr 28;80(4):837-844. doi: 10.1021/acs.jnatprod.6b00676. Epub 2017 Feb 16.
Six new fusicoccane-type diterpenoids (2-7) were isolated from the fermentation broth of Streptomyces violascens, which was isolated from Ailuropoda melanoleuca (giant panda) feces. The structures of these new compounds were elucidated by a detailed spectroscopic data and X-ray crystallographic analysis. Compounds 5-7 demonstrated cytotoxicity against five human cancer cell lines, with IC values ranging from 3.5 ± 0.7 to 14.1 ± 0.8 μM. Cell adhesion, migration, and invasion assays showed that 6 inhibited the migration and invasion of human hepatocellular carcinoma SMMC7721 cells in a dose-dependent manner. Through further investigation, it was revealed that 6 inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in addition to down-regulating the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels to influence the migration and invasion of cancer cells.
从大熊猫粪便中分离到的紫色链霉菌发酵液中分离得到了 6 个新的 fusicoccane 型二萜类化合物（2-7）。通过详细的光谱数据分析和 X 射线晶体学分析阐明了这些新化合物的结构。化合物 5-7 对 5 个人类癌细胞系表现出细胞毒性，IC 值范围为 3.5±0.7 至 14.1±0.8 μM。细胞黏附、迁移和侵袭实验表明，6 以剂量依赖的方式抑制人肝癌 SMMC7721 细胞的迁移和侵袭。通过进一步研究发现，6 抑制基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的酶活性，同时下调 MMP-2 和 MMP-9 在蛋白质和 mRNA 水平的表达，从而影响癌细胞的迁移和侵袭。
