title: Xanthohumol induces different cytotoxicity and apoptotic pathways in malignant and normal astrocytes.
abstract: Cytotoxicity and the mechanisms of cell death induced by xanthohumol (XN) were compared in normal and cancerous human cells as the differences may be relevant for the potential use of XN in cancer therapy. The cancer cells seemed to be more susceptible to the cytotoxicity of XN than normal cells, but a significant difference was observed only in astrocytic cells. XN induced a higher rate of apoptosis in glioblastoma cells than in normal astrocytes, which was associated with activation of p53 and an elevated Bax/Bcl-2 ratio in glioblastoma cells, indicating an intrinsic caspase-dependent apoptotic pathway. In contrast, a reduced Bax/Bcl-2 ratio was observed in normal human astrocytes. This was also associated with higher expression of the cell cycle inhibitor, p21, in glioblastoma cells than in normal astrocytes. In addition, at a lower, non-cytotoxic concentration, XN partially inhibited the invasiveness of glioblastoma cells. Due to the selective sensitivity of astrocytic cells to XN, this compound should be studied further as a candidate for adjuvant therapy in the treatment of glioma.
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, SI-1000, Ljubljana, Slovenia. irena.zajc@nib.si
authors.forename: I
authors.initials: I
authors.lastname: Zajc
authors.forename: M
authors.initials: M
authors.lastname: Filipič
authors.forename: T T
authors.initials: TT
authors.lastname: Lah
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D011427:Propiophenones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D011427:Propiophenones; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C104536:xanthohumol