Anti-angiogenic activity of triptolide in anaplastic thyroid carcinoma is mediated by targeting vascular endothelial and tumor cells.
Triptolide is confirmed to suppress angiogenesis of anaplastic thyroid carcinoma. Here we further expound the precise mechanism involved in this activity. Triptolide downregulated nuclear factor kappa B (NF-kappaB) pathway and its targeting genes associated with endothelial cell mobilization in human umbilical vein endothelial cells (HUVECs) and impaired VEGF expression in thyroid carcinoma TA-K cells. Furthermore, both triptolide and the conditioned medium from triptolide-treated TA-K cells (CMT) significantly attenuated proliferation, migration and tube formation of HUVECs. In vivo, triptolide inhibited TA-K cell-induced tumor growth, vascular formation and VEGF expression. Our data establish that triptolide inhibits tumor angiogenesis by the dual action on vascular endothelial cells and tumor cells, thus providing a novel and overall explanation for the anti-angiogenesis action of triptolide. The multicellular targets emphasize triptolide as a high-performance and potential angiogenesis inhibitor.
Zhu
Wenbo
W
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
He
Songmin
S
Li
Yan
Y
Qiu
Pengxin
P
Shu
Minfeng
M
Ou
Yanqiu
Y
Zhou
Yuehan
Y
Leng
Tiandong
T
Xie
Jun
J
Zheng
Xiaoke
X
Xu
Dong
D
Su
Xingwen
X
Yan
Guangmei
G
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004224:Diterpenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004852:Epoxy Compounds / Q000008:administration & dosage; D006801:Humans; D010616:Phenanthrenes / Q000008:administration & dosage*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide