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E35 ablates acute leukemia stem and progenitor cells in vitro and in vivo
Author(s) -
Chen Yingyu,
Zheng Jing,
Gan Donghui,
Chen Yanxin,
Zhang Na,
Chen Yuwen,
Lin Zhenxing,
Wang Wenfeng,
Chen Haijun,
Lin Donghong,
Hu Jianda
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29457
Subject(s) - stem cell , leukemia , haematopoiesis , progenitor cell , cancer research , in vivo , microbiology and biotechnology , chemistry , biology , immunology
Abstract Leukemia stem cells (LSCs) have critical functions in acute leukemia (AL) pathogenesis, participating in its initiation and relapse. Thus, identifying new molecules to eradicate LSCs represents a high priority for AL management. This work identified E35, a novel Emodin derivative, which strongly inhibited growth and enhanced apoptosis of AL stem cell lines, and primary stem and progenitor cells from AL cases, while sparing normal hematopoietic cells. Furthermore, functional assays in cultured cells and animals suggested that E35 preferentially ablated primitive leukemia cell populations without impairing their normal counterparts. Moreover, molecular studies showed that E35 remarkably downregulated drug‐resistant gene and dramatically inhibited the Akt/mammalian target of rapamycin signaling pathway. Notably, the in vivo anti‐LSC activity of E35 was further confirmed in murine xenotransplantation models. Collectively, these findings indicate E35 constitutes a novel therapeutic candidate for AL, potentially targeting leukemia stem and progenitor cells.