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Biologic activity of triptolide in t(8;21) acute myeloid leukemia cells |
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| Authors: | Gui-Sheng Zhou Zheng HuHai-Tong Fang Feng-Xiang ZhangXiao-Fen Pan Xiao-Qin ChenAn-Mei Hu Ling XuGuang-Biao Zhou |
| Institution: | a Laboratory of Molecular Carcinogenesis and Targeted Therapy for Cancer, Guangzhou Institute of Biomedicine and Health & State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, China b School of Life Sciences, University of Science and Technology of China, Hefei, China c Department of Hematology, the Cancer Hospital, Sun Yat-sen University, Guangzhou, China d The Second Xiangya Hospital, Central-South University, Changsha, China e The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China |
| Abstract: | Triptolide is a compound isolated from the traditional Chinese medicinal herb Tripterygium wilfordii that shows potent anti-tumor activities, but its effects on acute myeloid leukemia with t(8;21) remain unclear. Here we report that triptolide inhibits cell proliferation and induces apoptosis in a dose- and time-dependent manner of t(8;21)-bearing Kasumi-1, SKNO-1 and CD34+ cells harvested from bone marrow samples of patients with t(8;21) leukemia. We show that triptolide triggers cleavage of the resultant AML1-ETO fusion protein of t(8;21), and causes downregulation of C-KIT followed by inhibition of JAK-STAT signaling. Triptolide downregulates p65 and inhibits the DNA-binding activity of NF-κB. Our data indicate that triptolide might be an effective agent for t(8;21) leukemia. |
| Keywords: | Triptolide Acute myeloid leukemia (AML) t(8 21) AML1-ETO C-KIT JAK-STAT NF-κB |
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