marchantin-c and Glioma

This study aimed to examine the effects of marchantin C and fucoidan on angiogenesis induced by glioma cells and monocytes, and to elucidate the role of sFlt-1 in this process.. T98G glioma cells and THP1 monocytes were pretreated with marchantin C or fucoidan, respectively. Conditioned media were used for endothelial cell tube formation assay and detection of sFlt-1 by ELISA. Depletion of sFlt-1 was achieved by a neutralizing antibody to assess its role in the process.. Marchantin C inhibited angiogenesis induced by T98G cells while fucoidan inhibited both T98G and THP1 cell-induced angiogenesis. In all three groups in which angiogenesis was inhibited, sFlt-1 level in the supernatants was elevated. Pretreatment of the conditioned media with sFlt-1 antibody restored the inhibited angiogenesis to a certain degree.. This study suggested for the first time that marchantin C and fucoidan could significantly inhibit angiogenesis induced by glioma cells or monocytes. Up-regulation of sFlt-1 played an important role in this process.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Bibenzyls; Cell Line; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Glioma; Humans; Monocytes; Neovascularization, Pathologic; Phenyl Ethers; Polysaccharides; Tumor Microenvironment; Up-Regulation; Vascular Endothelial Growth Factor Receptor-1

Cancer cell migration is a leading cause of tumor recurrence and treatment failure. Previously, we reported that marchantin C exhibited promising antitumor activity by inducing microtubule depolymerization and apoptosis. In the present study, we investigated the effect of marchantin C on inhibition of migration in T98G and U87 cells. The scratch-induced migration, Boyden chamber and cell invasion assays were applied to determine that the migrating capacity and invasiveness of these glioma cell lines were inhibited when exposed to marchantin C at a low concentration. There are no obvious signs of apoptosis with this dose. Western blot analyses confirmed that MMP-2, a key role in cancer cell migration, was reduced after incubation with marchantin C in both glioma cell lines. In addition, signaling pathway investigations demonstrated that ERK/MAPK might be involved in MMP-2 downregulation, rather than the AKT/PI3K or JAK/STAT3 pathways. Moreover, marchantin C potently suppressed angiogenesis activity in vivo by CAM assay. This is the first study to demonstrate that marchantin C can inhibit glioma cell migration and invasiveness.

Topics: Antineoplastic Agents; Apoptosis; Bibenzyls; Brain Neoplasms; Catechols; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ethers, Cyclic; Glioma; Humans; Matrix Metalloproteinase 2; Neoplasm Invasiveness; Phenyl Ethers; Proto-Oncogene Proteins c-akt; Signal Transduction; STAT3 Transcription Factor

Macrocyclic bisbibenzyls, a class of characteristic components derived from liverworts, are attracting more and more attention because of their wide range of biological significance, including anti-bacterial, anti-fungus, anti-oxidation and cytotoxicity. Herein, we investigated the pro-apoptotic effect of marchantin C on human glioma A 172 cells. The results demonstrated that marchantin C conferred dose-dependent inhibitory effects onto cell growth, viability and colony formation ability of A 172 cells. Morphological observation and DNA laddering assay showed that marchantin C-treated A172 cells displayed outstanding apoptosis characteristics, such as nuclear fragmentation, the appearance of membrane-enclosed apoptotic bodies and DNA laddering fragment. Moreover, flow cytometric detection of phosphatidylserine externalization indicated that marchantin C-induced apoptosis occurred in a dose-dependent manner. RT-PCR and western blot assay further substantiated that marchantin C, as a promising pro-apoptotic agent, had strong effects to induce A172 cell apoptosis, suggesting that the action was achieved through up-regulating Bax and down-regulating Bcl-2.

Topics: Apoptosis; bcl-2-Associated X Protein; Bibenzyls; Catechols; Cell Line, Tumor; Cell Proliferation; Ethers, Cyclic; Glioma; Humans; Phenyl Ethers; Proto-Oncogene Proteins c-bcl-2