A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-kappa B pathway.
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.
Zhu
Wenbo
W
Department of Pharmacology, Zhong-shan Medical College, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Ou
Yanqiu
Y
Li
Yan
Y
Xiao
Ru
R
Shu
Minfeng
M
Zhou
Yuehan
Y
Xie
Jun
J
He
Songmin
S
Qiu
Pengxin
P
Yan
Guangmei
G
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
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide