ABSTRACT
The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet the molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Over-expression of PIAS3 effectively changes cell shape and inhibits GBM cell migration. We focused on the molecular target(s) of PIAS3 stimulated sumoylation, which play an important role in the inhibition of GBM cell motility. Here we report, through the immunoprecipitation with SUMO1 antibody, followed by proteomic analysis, the identification of vimentin (vimentin354), a nuclear component in GBM cells, as the main target of sumoylation promoted by PIAS3.
Subject(s)
Brain Neoplasms/pathology , Cell Movement/genetics , Glioma/pathology , Molecular Chaperones/physiology , Protein Inhibitors of Activated STAT/physiology , Sumoylation/physiology , Vimentin/metabolism , Adenoviridae/genetics , Amino Acid Sequence , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Line, Tumor , Down-Regulation/genetics , Down-Regulation/physiology , Glioma/genetics , Glioma/metabolism , Humans , Immunoprecipitation , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Molecular Sequence Data , Protein Inhibitors of Activated STAT/genetics , Protein Inhibitors of Activated STAT/metabolism , Proteomics , SUMO-1 Protein/metabolism , Sumoylation/genetics , Transfection , Vimentin/chemistryABSTRACT
Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.
