7-3--dihydroxy-4--methoxyisoflavone and Glioblastoma

The antitumor effect of calycosin has been widely studied, but the targets of calycosin against glioblastomas are still unclear. In this study we focused on revealing c-Met as a potential target of calycosin suppressing glioblastomas. In this study, suppressed-cell proliferation and cell invasion together with induced-cell apoptosis appeared in calycosin-treated U251 and U87 cells. Under treatment of calycosin, the mRNA expression levels of Dtk, c-Met, Lyn and PYK2 were observed in U87 cells. Meanwhile a western blot assay showed that c-Met together with matrix metalloproteinases-9 (MMP9) and phosphorylation of the serine/threonine kinase AKT (p-AKT) was significantly down-regulated by calycosin. Furthermore, overexpressed c-Met in U87 enhanced the expression level of MMP9 and p-AKT and also improved cell invasion. Additionally, the expression levels of c-Met, MMP9 and p-AKT were inhibited by calycosin in c-Met overexpressed cells. However, an AKT inhibitor (LY294002) only effected on MMP9 and p-AKT, not on c-Met. These data collectively indicated that calycosin possibility targeting on c-Met and exert an anti-tumor role via MMP9 and AKT.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromones; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Isoflavones; Matrix Metalloproteinase 9; Morpholines; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-met; Signal Transduction

In this study, we investigated the potential anticancer effects of calycosin against human glioblastoma cells, including the impacts on cell proliferation, apoptosis, and cell cycle distribution. We further studied its inhibitory activity on migration and invasion in U87 and U251 cells. Furthermore, transforming growth factor beta-mediated reductions of mesenchymal-associated genes/activators, matrix metalloproteinases-2, and -9 were detected in this process. Administration of calycosin in a glioblastoma xenograft model showed that calycosin could not only reduce tumor volume but also suppress transforming growth factor beta as well as its downstream molecules. These results revealed calycosin as a potential antitumor agent in human glioblastoma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Glioblastoma; Humans; Infant; Isoflavones; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasms, Experimental; Structure-Activity Relationship; Transforming Growth Factor beta; Tumor Cells, Cultured