Division of Marine Bioscience, College of Ocean Science and Technology, Korea Maritime and Ocean University, Busan 49112, Korea.
Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University, Baegyang-daero 700beon-gil 140, Sasang-gu, Busan 46958, Korea.
Molecules. 2019 Feb 8;24(3):604. doi: 10.3390/molecules24030604.
The current study investigated the ability of two secoiridoids, GL-3 () and oleonuezhenide (), isolated from the fruits of to inhibit MMP-2 and -9 activity in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 human fibrosarcoma cells. Both compound and were able to exert lowered gelatin digestion activity for MMP-2 and -9 tested by gelatin zymography via suppressing the release of MMPs to culture medium according to ELISA results. Treatment with compounds was also able to suppress the expression of both mRNA and protein levels of MMP-2 and -9. Action mechanism behind the MMP inhibitory effect of the compounds was suggested to be via MAPK pathway indicated by decreased levels of phosphorylated p38, ERK and JNK proteins evaluated employing immunoblotting. Compound was shown to be slightly more active to inhibit MMP-2 and -9, however, compound showed more regular dose-dependency during inhibition. In conclusion, this study suggested that GL-3 and oleonuezhenide were notable natural origin potent MMP inhibitors and could serve as lead compounds for development of anti-invasive MMP inhibitors against tumor metastasis.
本研究考察了从 果实中分离得到的两种环烯醚萜苷 GL-3()和橄榄苦苷（）抑制佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的 HT-1080 人纤维肉瘤细胞中 MMP-2 和 MMP-9 活性的能力。通过 ELISA 结果显示，化合物和均能通过抑制 MMPs 向培养基中的释放，降低明胶酶谱法检测到的 MMP-2 和 MMP-9 的明胶消化活性。化合物处理还能够抑制 MMP-2 和 MMP-9 的 mRNA 和蛋白水平的表达。通过免疫印迹评估，MAPK 途径的降低表明化合物的 MMP 抑制作用的作用机制。化合物 对抑制 MMP-2 和 MMP-9 的活性略高，但在抑制过程中，化合物 显示出更规律的剂量依赖性。总之，本研究表明 GL-3 和橄榄苦苷是具有显著抑制 MMP 活性的天然来源化合物，可作为开发抗侵袭性 MMP 抑制剂以抑制肿瘤转移的先导化合物。
