PT  - JOURNAL ARTICLE
AU  - Wenbo Zhu
AU  - Yanqiu Ou
AU  - Yan Li
AU  - Ru Xiao
AU  - Minfeng Shu
AU  - Yuehan Zhou
AU  - Jun Xie
AU  - Songmin He
AU  - Pengxin Qiu
AU  - Guangmei Yan
TI  - A Small-Molecule Triptolide Suppresses Angiogenesis and Invasion of Human Anaplastic Thyroid Carcinoma Cells via Down-Regulation of the Nuclear Factor-κB Pathway
AID  - 10.1124/mol.108.052605
DP  - 2009 Apr 01
TA  - Molecular Pharmacology
PG  - 812--819
VI  - 75
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/75/4/812.short
4100  - http://molpharm.aspetjournals.org/content/75/4/812.full
SO  - Mol Pharmacol2009 Apr 01; 75
AB  - 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-κB (NF-κB) 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-κB 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. The American Society for Pharmacology and Experimental Therapeutics