Dataset Information

Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells.

ABSTRACT: Several studies have indicated that ?-mangostin exerts anti-metastasis and anti-subsistence effects on several types of cancer cells. Especially, the anti-metastatic effect of ?-mangostin on cancer cells is a prospective function in cancer treatment. However, the metastasis process is complicated, and includes migration, invasion, intravasation, and extravasation; thus, the main target of anti-metastatic effect of ?-mangostin is not known. In this study, we investigated the effects of ?-mangostin on the invasion, subsistence, and migration of lung cancer cells under co-culture conditions with normal cells and regular mono-culture conditions. We found that ?-mangostin killed the lung cancer and normal cells in a dose-dependent manner. Furthermore, the alteration in the surface mechanical properties of cells was examined by using atomic force microscopy. Although the ?-mangostin concentrations of 5 and 10 µM did not affect the short-term cell viability, they considerably decreased the Young's modulus of lung cancer cells implying a decline in cell surface actin cytoskeletal properties. Additionally, these concentrations of ?-mangostin inhibited the migration of lung cancer cells. In co-culture conditions (cancer cells with normal cells), the invasive activities of cancer cells on normal cells were discernibly observed, and was inhibited after treatment with 5 and 10 µM of ?-mangostin. Taken together, ?-mangostin suppressed the subsistence of lung cancer cells and displayed anti-metastatic activities by inhibiting the migration and invasion, and reducing the actin cytoskeleton of cancer cells. Our findings suggest that ?-mangostin could be a potential therapeutic agent for cancer treatment.

SUBMITTER: Phan TKT

PROVIDER: S-EPMC6022730 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells.

Phan Thi Kieu Trang TKT Shahbazzadeh Fahimeh F Pham Thi Thu Huong TTH Kihara Takanori T

PeerJ 20180625

Several studies have indicated that α-mangostin exerts anti-metastasis and anti-subsistence effects on several types of cancer cells. Especially, the anti-metastatic effect of α-mangostin on cancer cells is a prospective function in cancer treatment. However, the metastasis process is complicated, and includes migration, invasion, intravasation, and extravasation; thus, the main target of anti-metastatic effect of α-mangostin is not known. In this study, we investigated the ...[more]

PMID: 29967723

Similar Datasets

Project description:Tumors and the tumor microenvironment produce multiple growth factors that influence cancer cell behavior via various signal transduction pathways. Growth factors, like transforming growth factor β (TGFβ) and epidermal growth factor (EGF), have been shown to induce proliferation, migration, and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, the similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of treating A549 lung adenocarcinoma cells with TGFβ, EGF, and both in combination by applying videomicroscopy, functional assays, immunoblotting, real-time PCR, and proteomics. Treatment with both factors stimulated A549 migration to a similar extent, but with different kinetics. The combination had an additive effect. EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway. However, this pathway was dispensable for TGFβ-induced migration, despite a strong activation of this pathway by TGFβ. Proteome analysis (data are available via ProteomeXchange with identifier PXD023024) revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF. Further, only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF, in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, TGFβ treatment significantly increased the invasive capacity of A549 cells, while EGF treatment did not. Moreover, the addition of EGF failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF can partly compensate for each other for stimulation of cell migration, but abrogation of TGFβ signaling may be more suitable to suppress cell invasion.

Project description:The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated. Human lung adenocarcinoma A549 cells were transfected with synthetic specific siRNAs targeting a fragment of the FGFR3 gene (namely, siRNA-855, siRNA-1447 and siRNA-2076) or with negative control (NC) siRNA. Cells were divided into five groups (A, siRNA-855 group; B, siRNA-1447 group; C, siRNA-2076 group; D, NC-siRNA group; and E, blank control group). The effect of the above siRNAs targeting FGFR3 on the invasion capacity of A549 cells was detected by Transwell assay. siRNAs against FGFR3 were transfected into A549 cells with by Lipofectamine® 2000, and the expression levels of FGFR3, E-cadherin and MMP9 were measured by reverse transcription-quantitative polymerase chain reaction and western blot assay. The experimental findings indicated that the expression levels of FGFR3 and MMP9 were significantly reduced in the siRNA-FGFR3-transfected groups (A-C groups), compared with those in the D and E groups (P<0.01). In addition, the expression levels of E-cadherin were markedly elevated in the A-C groups, compared with those in the D and E groups (P<0.01). There was no significant difference in E-cadherin expression between the A-C groups, or between the D and E groups (P>0.05). These results indicated that siRNA-FGFR3 was able to decrease the invasiveness of A549 cells, inhibit the expression of MMP9 and increase the expression of E-cadherin by downregulating the expression of FGFR3. Taken together, the results of the present study indicated that the upregulation of E-cadherin expression and the downregulation of MMP9 expression are able to inhibit the migration of A549 cells, and siRNA silencing FGFR3 acts as a tumor suppressor in these cells.

Project description:BackgroundLung cancer is the most prevalent and deadly tumors around the world. Here we aimed to investigate the effect of wogonoside (also called baicalin) on the invasion and migration of lung cancer A549 cells and angiogenesis in xenograft tumors in nude mice.MethodsA549 cells of lung cancer were treated with different doses of wogonoside. After 24 h, CCK8 was used to detect the survival rate of cells. The non-toxic doses of wogonoside (0, 10, 25, and 50 µM) were selected for subsequent experiments. Transwell and scratch assays were used to detect invasion and migration. The number of microtubule nodules was detected by microtubule formation experiment, and the expressions of VEGF, E-cadherin, N-cadherin, and Vimentin were detected by Western blotting. BALB/c nude mice were subcutaneously injected with lung cancer A549 cells to establish the xenograft model, followed by intraperitoneal injection of 80 mg/kg of wogonoside. After 30 days, tumor volume was measured, and the levels of VEGF and vimentin were detected with immunohistochemistry. The level of CD34 was determined by flow sorting.ResultsA549 cell survival decreased in a concentration-dependent manner, with the survival rate significantly reduced when the concentration of wogonoside exceeded 100 µM (P<0.05). A549 cell invasion and the number of microtubule nodules were significantly lower in the wogonoside 20 µM and the wogonoside 50 µM groups (P<0.05) compared with the wogonoside 0 µM group, while the rate of scratch closure and the protein levels of VEGF, N-cadherin, and Vimentin were all significantly reduced (P<0.05), and the expression level of E-cadherin was significantly increased (P<0.05). Compared with the control group, the tumor volumes of wogonoside (80 mg/kg) treated mice were significantly reduced after 30 days (P<0.05), and the levels of VEGF and vimentin positive cells were significantly reduced (P<0.05), as was the level of CD34 (P<0.05).ConclusionsWogonoside can inhibit the invasion and migration of lung cancer A549 cells and angiogenesis of xenograft tumors in nude mice.

Dataset Information

Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells.

Publications

Alpha-mangostin inhibits the migration and invasion of A549 lung cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets