Shikonin Derivative DMAKO-05 Inhibits Akt Signal Activation and Melanoma Proliferation

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• 作者：Yao-yao Yang ; Hui-qiong He ; Jia-hua Cui ; Yun-juan Nie ; Ya-xian Wu ; Rui Wang ; Gang Wang ; Jun-Nian Zheng ; Richard D. Ye ; Qiong Wu ; Shao-shun Li and Feng Qian
• 刊名：Chemical Biology & Drug Design
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：87
• 期：6
• 页码：895-904
• 全文大小：994K
• ISSN：1747-0285

文摘

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 herb Lithospermun 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.