Sulforaphane regulates the proliferation of leukemia stem-like cells via Sonic Hedgehog signaling pathway
Sulforaphane regulates the proliferation of leukemia stem-like cells via Sonic Hedgehog signaling pathway
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萝卜硫素通过 Sonic Hedgehog 信号通路调节白血病干细胞样细胞的增殖
DOI：
10.1016/j.ejphar.2022.174824
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发表时间：
2022
影响因子：
5
通讯作者：
Peijun Liu
中科院分区：
文献类型：
--
作者：
Fanping Wang;Xiaoyu Huang;Yanwei Sun;Zhixin Li;Ruili Sun;Tiesuo Zhao;Mingyong Wang;Chunxia Yan;Peijun Liu
萝卜硫素(SFN)是西兰花/西兰花芽中的主要成分，在多种肿瘤中具有良好的抗癌作用，但SFN是否影响急性白血病尚不清楚。由于白血病干细胞的自我更新能力，急性白血病复发率较高。本研究旨在探讨三七总皂苷对急性髓系白血病细胞白血病干细胞增殖的影响及其相关分子机制。我们发现SFN在体内外对白血病干细胞的增殖均有抑制作用。同时，我们观察到SFN对白血病细胞的干细胞特性有调节作用。SFN处理后，Sonic Hedgehog(Shh)信号通路中的关键成员在转录和蛋白水平上的表达均显著降低。为了进一步确定Shh信号分子机制在SFN介导的LSCs自我更新能力中的作用，我们随后在白血病细胞中操纵Shh基因，要么通过慢病毒载体转导过表达该基因，要么通过siRNA敲除该基因。结果表明，SFN对Shh高表达细胞的增殖抑制作用强于Shh下调细胞，提示SFN通过影响Shh信号通路负向调控白血病干细胞的增殖。综上所述，这些结果表明SFN是一种有效的抗白血病药物，它通过调节Shh信号通路而抑制白血病干细胞的增殖。
Sulforaphane (SFN), the main ingredient in broccoli/broccoli sprouts, has a good anticancer effect in a wide variety of tumors, but whether SFN affects acute leukemia is not elucidated. Due to the self-renewal capability for leukemia stem cells, acute leukemia has a high relapse rate. This study explored the effects and related molecular mechanisms of SFN on the proliferation of leukemia stem-like cells in acute myeloid leukemia cells. We found that SFN inhibited the proliferation of leukemia stem-like cells invitroand invivo. Meanwhile, we observed that SFN could regulate the stem characteristic of leukemia cells. After SFN treatment, the expression of the key players in the Sonic Hedgehog (Shh) signaling pathway was significantly decreased at the transcriptional and protein levels. To further determine the contribution of the Shh signaling molecular mechanism to SFN-mediated self-renewal capability of LSCs, we then manipulated the Shh gene in the leukemia cells to either overexpress the gene using lentiviral vector transduction or knockdown the gene via siRNA. The results demonstrated that SFN suppressed proliferation in Shh-overexpressed cells more than in Shh-downregulated cells, suggesting that SFN negatively modulates proliferation of leukemia stem-like cells via affecting the Shh signaling pathway. Altogether, these results suggest that SFN is a potent anti-leukemia agent that has inhibitory effects on leukemia stem-like cells' proliferation by regulating the Shh signaling pathway.