Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism.
Triptolide, a traditional anti-inflammatory and anti-immunodepressive agent, has been reported to exert anti-neoplastic activity on several human tumor cell lines. This study investigates the pro-apoptotic function and the functional mechanism of triptolide on anaplastic thyroid carcinoma (ATC) cells. Experiments presented here demonstrated that triptolide had dose-dependent effects on cell viability of human ATC cell line TA-K cells through inducing cell apoptosis. In the molecular level, triptolide did not successfully initiate p53 signaling pathway, but downregulated the nuclear factor kappaB (NF-kappaB) pathway. Our studies suggest that triptolide functions as an effective apoptotic inducer in a p53-independent, but NF-kappaB-dependent mechanism, thus providing a promising agent for tumor types with p53 mutation/deletion.
Zhu
Wenbo
W
Department of Pharmacology, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou, PR China.
Hu
Haiyan
H
Qiu
Pengxin
P
Yan
Guangmei
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C001899:triptolide