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.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Zhu W,Ou Y,Li Y,Xiao R,Shu M,Zhou Y,Xie J,He S,Qiu P,Yan Gdoi
10.1124/mol.108.052605subject
Has Abstractpub_date
2009-04-01 00:00:00pages
812-9issue
4eissn
0026-895Xissn
1521-0111pii
mol.108.052605journal_volume
75pub_type
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