Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating β-catenin activation and EMT pathways

Glioblastoma(GBM)is a highly vascularized malignant brain tumor with poor clinical outcomes.Vasculogenic mimicry(VM)formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy.To date,there is still a lack of effective drugs that target VM formation in GBM.In the present study,we evaluated the effects of the plant cyclopeptide moroidin on VM formed by GBM cells and investigated its underlying molecular mechanisms.Moroidin significantly suppressed cell migration,tube formation,and the expression levels ofα-smooth muscle actin and matrix metalloproteinase-9 in human GBM cell lines at sublethal concentrations.The RNA sequencing data suggested the involvement of the epithelialmesenchymal transition(EMT)pathway in the mechanism of moroidin.Exposure to moroidin led to a concentration-dependent decrease in the expression levels of the EMT markers N-cadherin and vimentin in GBM cells.Moreover,moroidin significantly reduced the level of phosphorylated extracellular signal-regulated protein kinase(p-ERK)and inhibited the activation of β-catenin.Finally,we demonstrated that the plant cyclopeptide moroidin inhibited VM formation by GBM cells through inhibiting the ERK/β-catenin-mediated EMT.Therefore,our study indicates a potential application of moroidin as an anti-VM agent in the treatment of GBM.

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F

As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.