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

Abstract

Abstract. 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. IntroductionCancer is a leading cause of mortality; ~8.2 million people worldwide succumbed to cancer-associated mortality in 2012, with lung cancer accounting for ~1.59 million cases of mortality, or ~20% of the total (1). Lung cancer cell metastasis is a primary cause of mortality and those that experience it have a mortality rate of ≥90% (2). When it metastasizes, lung cancer has a 95% chance of affecting local lymph nodes and an 80% chance of affecting other organs (3,4). Thus, in clinical terms, the overall 5-year survival rate from the time of diagnosis to mortality for patients with lung cancer undergoing treatment is only 10-15% (5). Cancer cell metastasis is a complex multistep process involving invasion and migration (6-8). Matrix metalloproteinases (MMPs) are zinc/calcium-dependent endopeptidases involved in the degradation of the extracellular matrix, two examples of which are MMP-2 and -9 (7,9). MMP-2 is a notable factor in the development of tumor metastasis (7,10). MMP-2 is highly expressed in malignant tumors and serves a key role in cancer invasion and angiogenesis (7,11). The inhibition of MMP-2 is, therefore, an effective strategy for preventing tumor cell metastasis (11,12). The NME/NM23 nucleoside diphosphate kinase 1 (NM23) gene was first identified in the murine melanoma cell line exhibiting high metastatic activity; increasing the expression of this gene may also reduce the metastatic activity of tumor cel...

Anti-Inflammatory Effect of Erinacine C on NO Production Through Down-Regulation of NF-κB and Activation of Nrf2-Mediated HO-1 in BV2 Microglial Cells Treated with LPS

“…Cell culture was performed as described previously [2,41]. Briefly, the BV2 microglial cells (a gift from Dr. Yuh-Chiang Shen, National Research Institute of Chinese Medicine, Taipei, Taiwan) were cultured in DMEM medium containing 10% ( v / v ) fetal bovine serum (FBS), 0.37% ( w / v ) NaHCO 3 , penicillin (100 units/mL), and streptomycin (100 μg/mL) at 37 °C in a humidified incubator under 5% CO 2 and 95% air.…”

“…The cell growth was assayed as described in a previous study by Chuang et al [41]. BV2 cells were plated in 24-well plates at a density of 1 × 10 5 cells/well and grown for 24 h. Different concentrations of EC were then added to the cells to reach final concentrations of 0.1, 0.5, 1, 2.5, 5, and 10 µM in the presence of FBS.…”

“…Expression levels of NF-κB, IκB, p-IκBα, Keap-1, Nrf2, HO-1, and iNOS proteins were determined by western blotting. Western blot analysis was performed as described previously [41]. Briefly, the medium was removed and cells were lysed with 20% sodium dodecyl sulphate (SDS) containing 1 mM phenylmethylsulfonyl fluoride.…”

“…Statistical analysis was performed as described previously [41]. Values were expressed as means ± SD and analyzed using one-way ANOVA, followed by the application of Duncan’s Multiple Range Test for comparisons of group means.…”

3D Bioprinted Vascularized Tumour for Drug Testing

“…a size reduction of the MCTSs was observed in the isolinderalactone-treated samples as well ( Figure S4). Isolinderalactone is an extract from Lindera aggregata, which is a traditional Chinese herbal medicine [42]. The result suggests that the bioprinted blood vessel layer is suitable for interaction with multiple MCTSs (approximately 4-7) and can be widely used for testing various anti-cancer drugs.…”