Guaianolide Sesquiterpene Lactones, a Source To Discover Agents That Selectively Inhibit Acute Myelogenous Leukemia Stem and Progenitor Cells

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• 作者：Quan Zhang ; Yaxin Lu ; Yahui Ding ; Jiadai Zhai ; Qing Ji ; Weiwei Ma ; Ming Yang ; Hongxia Fan ; Jing Long ; Zhongsheng Tong ; Yehui Shi ; Yongsheng Jia ; Bin Han ; Wenpeng Zhang ; Chuanjiang Qiu ; Xiaoyan Ma ; Qiuying Li ; Qianqian Shi ; Haoliang Zhang ; Dongmei Li ; Jing Zhang ; Jianping Lin ; Lu-Yuan Li ; Yingdai Gao ; Yue Chen
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：October 25, 2012
• 年：2012
• 卷：55
• 期：20
• 页码：8757-8769
• 全文大小：647K
• 年卷期：v.55,no.20(October 25, 2012)
• ISSN：1520-4804

文摘

Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34⁺CD38^{鈥?/sup>) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches.}