AS1041, a Novel Synthesized Derivative of Marine Natural Compound Aspergiolide A, Arrests Cell Cycle, Induces Apoptosis, and Inhibits ERK Activation in K562 Cells.
AS1041, a Novel Synthesized Derivative of Marine Natural Compound Aspergiolide A, Arrests Cell Cycle, Induces Apoptosis, and Inhibits ERK Activation in K562 Cells.
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AS1041 是海洋天然化合物 Aspergiolide A 的新型合成衍生物，可抑制 K562 细胞的细胞周期、诱导细胞凋亡并抑制 ERK 激活
DOI：
10.3390/md15110346
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发表时间：
2017-11-04
期刊：
影响因子：
5.4
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Yuan F;Qiao L;Chen Y;Qi X;Liu Y;Li D;Gu Q;Li J;Liu M
AS 1041是一种新型的海洋天然化合物曲霉素A（ASP-A）的蒽醌内酯衍生物，具有新的结构骨架和显著的癌细胞毒性。为研究其细胞毒作用，我们对该化合物对人慢性粒细胞白血病细胞株K562的活性进行了评价，并探讨了其相关的分子机制。AS 1041对K562细胞的增殖和集落形成有明显的抑制作用。此外，AS 1041以浓度依赖性方式将细胞周期阻滞在G2/M期，并引起浓度和时间依赖性的凋亡诱导。此外，分子机制研究表明，AS 1041不定位于细胞核，不影响拓扑异构酶I和II。但是，AS 1041可以抑制细胞外信号调节激酶（ERK），并参与AS 1041诱导的细胞凋亡。结论：AS 1041对K562白血病细胞具有细胞毒性，其作用机制与细胞周期阻滞、诱导细胞凋亡和抑制ERK有关。这些结果表明，AS 1041是一种新型的ASP-A衍生物，对慢性粒细胞白血病细胞具有明显的细胞毒性，可能具有治疗癌症和白血病的潜力。
AS1041 is a novel synthesized anthraquinone lactone derivative of marine natural compound aspergiolide A (ASP-A) with new structure skeleton and marked cytotoxicity in cancer cells. To study its cytotoxicity in detail, we evaluated its activity on human K562 chronic myelogenous leukemia cells and investigated the related molecule mechanisms. AS1041 significantly inhibited the proliferation and colony formation of K562 cells. Moreover, AS1041 arrested cell cycle progression at G2/M phase in a concentration-dependent manner, and also caused concentration- and time-dependent induction of apoptosis. In addition, the molecular mechanisms investigation showed that AS1041 did not localize in the cellular nucleus and did not affect topoisomerases I or II. However, AS1041 could inactivate extracellular signal-regulated kinase (ERK) and contribute to AS1041-induced apoptosis. We concluded that AS1041 was cytotoxic to K562 leukemia cells and the cytotoxicity related to the cell cycle arrest, apoptosis induction, and ERK inhibition. These results implied that AS1041 was a novel derivative of ASP-A with significant cytotoxicity to chronic myelogenous leukemia cells and may have therapeutic potential for the treatment of cancer and leukemia.
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