title: Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma             through the NF-κB pathway.
abstract: Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.forename: Hua-Zi
authors.initials: HZ
authors.lastname: Xu
authors.forename: Shi-Zhou
authors.initials: SZ
authors.lastname: Yang
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Ying
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Hai-Xiao
authors.initials: HX
authors.lastname: Liu
authors.forename: Zhong-Qin
authors.initials: ZQ
authors.lastname: Lin
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Chen
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Cheng
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Shen
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000378:metabolism; D012516:Osteosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D016227:Benzoquinones; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D016328:NF-kappa B; D009842:Oligopeptides; C532637:SMAC peptide; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D053148:Caspase 3; C003466:thymoquinone