Triptolide inhibits Jak2 transcription and induces apoptosis in human myeloproliferative disorder cells bearing Jak2V617F through caspase-3-mediated cleavage of Mcl-1

Cancer Letters
Qi ChenJingxuan Pan

Abstract

The discovery of oncogene addiction in myeloproliferative disorders (MPDs) driven by the gain-of-function mutant Jak2V617F has attracted intense interest in targeted therapy for MPDs. In this report, we demonstrate that triptolide potently downregulated the transcription of Jak2 by inhibiting the activity of RNA polymerase. Triptolide inhibited the in vitro and in vivo growth of tumor cells harboring Jak2V617F. Triptolide induced abundant apoptosis with a prominent decline of Bcl-2, Bcl-X(L), survivin and Mcl-1. As well, triptolide induced caspase-3-dependent Mcl-1 cleavage, which may potentiate apoptosis. These findings suggest that triptolide is a promising agent to kill Jak2V617F-harboring cells.

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Citations

Nov 13, 2010·Experimental & Molecular Medicine·Haw-Young KwonYoung-Choon Lee
Jan 25, 2011·International Immunopharmacology·Qiuyan Liu
Sep 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Meili ZhangThomas A Waldmann
Jun 17, 2014·Journal of Ethnopharmacology·Xiao-Jiaoyang LiLu-yong Zhang
Jun 28, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zi LiuGuang-Biao Zhou
Sep 14, 2017·International Journal of Molecular Medicine·Ji-Hun Kim, Byoungduck Park

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