title: Effects of thymoquinone on isolated and cellular proteasomes.
abstract: Thymoquinone, a naturally derived agent, has been shown to possess antioxidant, antiproliferative and proapoptotic activities. In the present study, we explored thymoquinone effects on the proteasomal complex, the major system involved in the removal of damaged, oxidized and misfolded proteins. In purified 20S complexes, subunit-dependent and composition-dependent inhibition was observed, and the chymotrypsin-like and trypsin-like activities were the most susceptible to thymoquinone treatment. U87 MG and T98G malignant glioma cells were treated with thymoquinone, and 20S and 26S proteasome activity was measured. Inhibition of the complex was evident in both cell lines, but predominantly in U87 MG cells, and was accompanied by accumulation of ubiquitin conjugates. Accumulation of p53 and Bax, two proteasome substrates with proapoptotic activity, was observed in both cell lines. Our results demonstrate that thymoquinone induces selective and time-dependent proteasome inhibition, both in isolated enzymes and in glioblastoma cells, and suggest that this mechanism could be implicated in the induction of apoptosis in cancer cells.
authors.affiliation: University of Camerino, Italy. valentina.cecarini@unicam.it <valentina.cecarini@unicam.it>
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.forename: Luana
authors.initials: L
authors.lastname: Quassinti
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Blasio
authors.forename: Laura
authors.initials: L
authors.lastname: Bonfili
authors.forename: Massimo
authors.initials: M
authors.lastname: Bramucci
authors.forename: Giulio
authors.initials: G
authors.lastname: Lupidi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.forename: Matteo
authors.initials: M
authors.lastname: Mozzicafreddo
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eleuteri
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000302:isolation & purification / Q000378:metabolism; D061988:Proteasome Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D016227:Benzoquinones; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D046988:Proteasome Endopeptidase Complex; C003466:thymoquinone