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Oncol Lett. 2018 Apr;15(4):4690-4696. doi: 10.3892/ol.2018.7862. Epub 2018 Jan 25.

Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2 and up regulation of NM23-H1 expression in human lung cancer A549 cells.

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Department of Nutrition, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Department of Beauty Science, National Taichung University of Science and Technology, Taichung 40343, Taiwan, R.O.C.


Metastatic lung cancer is a leading cause of mortality and has a mortality rate of ≥90%. Isolinderalactone (ILL) is a sesquiterpene lactone compound that has been used in traditional Chinese medicine. Research has demonstrated that ILL has anti-inflammatory and anti-proliferative properties; however, to the best of our knowledge, studies investigating whether ILL can inhibit lung cancer cell metastasis have not been conducted. In the present study, 1-10 µM ILL was applied in the culturing of the A549 lung cancer cell line to investigate the effects of ILL on the invasion and migration of lung cancer cells, including whether the possible mechanisms of ILL are associated with the expression of matrix metalloproteinase (MMP)-2 and NME/NM23 nucleoside diphosphate kinase 1 (NM23-H1) genes. The results of the present study indicated that ILL inhibited the invasion and migration of the A549 cancer cells and exhibited a dose-response association. ILL also significantly inhibited the protein expression and activity of MMP-2 (P<0.05), exhibiting a trend similar to that of its invasion- and migration-associated properties. Further research revealed that ILL significantly increased the expression of NM23-H1 protein and inhibited the expression of β-catenin protein (P<0.05). The results of the present study is, to the best of our knowledge, the first to confirm that ILL can inhibit the invasion and migration of A549 cancer cells, with the possible mechanisms potentially involving the inhibition of MMP-2 and β-catenin protein expression resulting from the up regulation of NM23-H1 expression.


NME/NM23 nucleoside diphosphate kinase 1; invasion; isolinderalactone; lung cancer cells; matrix metalloproteinase-2; migration

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