A cardiac glycoside HTF-1 isolated from Helleborus thibetanus Franch displays potent in vitro anti-cancer activity via caspase-9, MAPK and PI3K-Akt-mTOR pathways
A cardiac glycoside HTF-1 isolated from Helleborus thibetanus Franch displays potent in vitro anti-cancer activity via caspase-9, MAPK and PI3K-Akt-mTOR pathways
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从Helleborus thibetanus Franch 中分离出的强心苷 HTF-1 通过 caspase-9、MAPK 和 PI3K-Akt-mTOR 途径显示出有效的体外抗癌活性
DOI：
10.1016/j.ejmech.2018.09.019
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发表时间：
2018-10-05
影响因子：
6.7
通讯作者：
Su, Yanfang
中科院分区：
文献类型：
--
作者：
Ma, Long;Meng, Yuanyuan;Su, Yanfang
从铁筷子中分离得到一个新的强心苷。中国特有植物，具有很强的抗癌活性。我们将其命名为HTF-1。通过使用体外细胞模型，我们发现HTF-1以浓度和时间依赖性方式诱导针对几种类型的癌细胞的凋亡。它能抑制癌细胞的增殖、迁移和侵袭。HTF-1导致S细胞周期停滞。进一步，我们已经确定HTF-1触发caspase-9依赖的凋亡途径和双链DNA断裂（DSB 5）。此外，HTF-1激活JNK，但抑制ERK和PI 3 K-Akt-mTOR通路。总之，上述机制有助于HTF-1的抗癌活性。在过去的几十年中，发现新的抗癌CG是罕见的。我们相信，我们的工作将丰富对CG的理解，也为基于天然产物的抗癌药物开发铺平道路。(C)2018 Elsevier Masson SAS。All rights reserved.
Experiments have been undertaken and for the first time, we have identified that a new cardiac glycoside (CG) isolated from Helleborus thibetanus Franch. a plant endemic to China, bears potent anti-cancer activity. We have named it as HTF-1. By using in vitro cell models, we have found that HTF-1 induces apoptosis against several types of cancer cells in a concentration- and time-dependent manner. It is able to inhibit cancer cell in proliferation, migration and invasion. HTF-1 causes S cell cycle arrest. Further-on, we have identified that HTF-1 triggers caspase-9 dependent apoptosis pathway and double strand DNA breaks (DSB5). Additionally, HTF-1 activates JNK, but suppresses ERK and PI3K-Akt-mTOR pathways. Collectively, the above-mentioned mechanisms contribute to the anti-cancer activity of HTF-1. It is rare to discover novel anti-cancer CG during the past couple of decades. We believe that our work will enrich the understanding of CGs; also, pave the way for natural product-based anti-cancer drug development. (C) 2018 Elsevier Masson SAS. All rights reserved.