title: A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-kappa B pathway.
abstract: Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies. Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis in vivo, and invasion in a Matrigel model in human ATC cell line TA-K cells at nanomolar concentrations. We further elucidate that triptolide inhibits the nuclear factor-kappaB (NF-kappaB) transcriptional activity via blocking the association of p65 subunit with CREB-binding protein (CBP)/p300 in the early stage and via decreasing the protein level of p65 in the late stage. Expression of the NF-kappaB targeting genes cyclin D1, vascular endothelial growth factor, and urokinase-type plasminogen activator is significantly reduced by triptolide in both TA-K and 8505C human ATC cell lines, which are well known to be critical for proliferation, angiogenesis, and invasion in solid tumors. Our findings suggest that triptolide may function as a small molecule inhibitor of tumor angiogenesis and invasion and may provide novel mechanistic insights into the potential therapy for human ATC.
authors.affiliation: Department of Pharmacology, Zhong-shan Medical College, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Ou
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ru
authors.initials: R
authors.lastname: Xiao
authors.forename: Minfeng
authors.initials: M
authors.lastname: Shu
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Songmin
authors.initials: S
authors.lastname: He
authors.forename: Pengxin
authors.initials: P
authors.lastname: Qiu
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D029757:Tripterygium
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide