title: Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma.
abstract: We provide evidence that thymoquinone (TQ), a natural compound isolated from Nigella sativa, induces growth inhibition and apoptosis in several primary effusion lymphoma (PEL) cell lines. Our data demonstrate that TQ treatment results in down-regulation of constitutive activation of AKT via generation of reactive oxygen species (ROS) and it causes conformational changes in Bax protein, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and polyadenosine 5'-diphosphate ribose polymerase cleavage, leading to caspase-dependent apoptosis. Pretreatment of PEL cells with N-acetylcysteine, a scavenger of ROS, prevented TQ-mediated effects. In addition, subtoxic doses of TQ sensitized PEL cells to TRAIL via up-regulation of DR5. Altogether, these findings demonstrate that TQ is a potent inducer of apoptosis in PEL cells via release of ROS. They also raise the possibility that incorporation of TQ in treatment regimens for primary effusion lymphomas may provide a novel approach to sensitizing malignant cells and provide a molecular basis for such future translational efforts.
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: Azhar R
authors.initials: AR
authors.lastname: Hussain
authors.forename: Maqbool
authors.initials: M
authors.lastname: Ahmed
authors.forename: Saeeda
authors.initials: S
authors.lastname: Ahmed
authors.forename: Pulicat
authors.initials: P
authors.lastname: Manogaran
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
authors.forename: Syed N
authors.initials: SN
authors.lastname: Alvi
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D006801:Humans; D020287:In Situ Nick-End Labeling; D054685:Lymphoma, Primary Effusion / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C003466:thymoquinone