Shikonin derivative DMAKO-05inhibits Akt signal activation and melanoma proliferation.
Shikonin derivative DMAKO-05inhibits Akt signal activation and melanoma proliferation.
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紫草素衍生物 DMAKO-05 抑制 Akt 信号激活和黑色素瘤增殖
DOI：
10.1111/cbdd.12722
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发表时间：
2016
影响因子：
3
通讯作者：
Feng Qian
中科院分区：
文献类型：
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作者：
Yao-yao Yang;Hui-qiong He;Jia-hua Cui;Yun-juan Nie;Ya-xian Wu;Rui Wang;Richard D. Ye;Qiong Wu;Shao-shun Li;Feng Qian
DMAKO-05（（S）-1-（（5E，8 E）-5，8-bis（hydroxyimino）-1，4-dimethoxy-5，8-dihydradaphthalen-2-yl）-4-methylpropanol-3-enyl 3-methylbutanoate）是紫草素的一个新的肟衍生物，紫草素是紫草的主要成分。在这里，我们报告了DMAKO-05对小鼠黑色素瘤细胞系B16 F0具有抗肿瘤活性。我们的研究表明，DMAKO-05不仅能抑制B16 F0的增殖和迁移，还能导致细胞周期停滞在G1期和细胞凋亡，其中DMAKO-05触发了线粒体介导的凋亡信号，包括caspase-9/3和PARP。响应于DMAKO-05处理，Akt介导的存活信号在B16 F0细胞中显著减弱。总的来说，DMAKO-05通过抑制Akt激活、诱导G1期阻滞和促进B16 F0细胞凋亡，对B16 F0细胞具有较强的细胞毒性。DMAKO-05可能作为黑色素瘤的潜在候选先导化合物。
DMAKO‐05((S)‐1‐((5E,8E)‐5,8‐bis(hydroxyimino)‐1,4‐dimethoxy‐5,8‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐enyl 3‐methylbutanoate) is a novel oxime derivative of shikonin, the major component extracted from Chinese herbLithospermun erythrorhizon. Here, we report that DMAKO‐05 had an antitumor activity against mouse melanoma cell line B16F0. Our studies indicated that DMAKO‐05 not only inhibited B16F0 proliferation and migration but also led to cell cycle arrest at G1 phase and cell apoptosis, in which DMAKO‐05 triggered mitochondrial‐mediated apoptosis signal including caspase‐9/3 and PARP. In response to DMAKO‐05 treatment, the Akt‐mediated survival signals were remarkably attenuated in B16F0 cells. Collectively, DMAKO‐05 has a strong cytotoxicity in B16F0 cells via inhibiting Akt activation, inducing G1 arrest, and promoting B16F0 cell apoptosis. DMAKO‐05 might serve as a potential candidate lead compound for melanoma.