RT Journal Article
SR Electronic
T1 A Small-Molecule Triptolide Suppresses Angiogenesis and Invasion of Human Anaplastic Thyroid Carcinoma Cells via Down-Regulation of the Nuclear Factor-κB Pathway
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 812
OP 819
DO 10.1124/mol.108.052605
VO 75
IS 4
A1 Wenbo Zhu
A1 Yanqiu Ou
A1 Yan Li
A1 Ru Xiao
A1 Minfeng Shu
A1 Yuehan Zhou
A1 Jun Xie
A1 Songmin He
A1 Pengxin Qiu
A1 Guangmei Yan
YR 2009
UL http://molpharm.aspetjournals.org/content/75/4/812.abstract
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