title: Quercetin and sorafenib as a novel and effective couple in programmed cell death induction in human gliomas.
abstract: The aim of the present study was to investigate the effect of sorafenib and quercetin on the induction of apoptosis and autophagy in human anaplastic astrocytoma (MOGGCCM) and glioblastoma multiforme (T98G) cell lines. In MOGGCCM cells, sorafenib initiated mainly apoptosis, mediated by the mitochondrial pathway with mitochondrial membrane permeabilization, cytochrome c release to the cytoplasm, and activation of caspase 9 and 3. Additional incubation with quercetin potentiated the pro-apoptotic properties of sorafenib. In T98G cells, autophagy was observed most frequently after the sorafenib treatment. It was accompanied by increased beclin 1 and LC3II expression. Administration of quercetin after the sorafenib treatment resulted in an increased number of autophagic cells. After simultaneous drug application, the level of autophagy was lower in favour of apoptosis. Inhibition of heat shock proteins expression by specific small interfering RNA significantly increased the sensitivity of both the cell lines to induction of apoptosis, but not autophagy. We demonstrated for the first time that sorafenib and quercetin are very effective programmed cell death inducers in T98G and MOGGCCM cells, especially in cells with blocked expression of heat shock proteins.
authors.affiliation: Department of Comparative Anatomy and Anthropology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland, jjgil@poczta.umcs.lublin.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakubowicz-Gil
authors.forename: Ewa
authors.initials: E
authors.lastname: Langner
authors.forename: Dorota
authors.initials: D
authors.lastname: Bądziul
authors.forename: Iwona
authors.initials: I
authors.lastname: Wertel
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001254:Astrocytoma / Q000188:drug therapy / Q000503:physiopathology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D005909:Glioblastoma / Q000188:drug therapy / Q000503:physiopathology; D005910:Glioma / Q000188:drug therapy* / Q000503:physiopathology; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018832:Molecular Chaperones; D009336:Necrosis / Q000139:chemically induced / Q000503:physiopathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010671:Phenylurea Compounds; D009536:Niacinamide; D011794:Quercetin; D000077157:Sorafenib