Thevebioside, the active ingredient of traditional Chinese medicine, promotes ubiquitin-mediated SRC-3 degradation to induce NSCLC cells apoptosis
Thevebioside, the active ingredient of traditional Chinese medicine, promotes ubiquitin-mediated SRC-3 degradation to induce NSCLC cells apoptosis
复制标题
中药活性成分Thevebioside促进泛素介导的SRC-3降解诱导NSCLC细胞凋亡
DOI：
10.1016/j.canlet.2020.08.011
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发表时间：
2020-11-28
期刊：
影响因子：
9.7
通讯作者：
Xu, Zihang
中科院分区：
文献类型：
--
作者：
Yao, Chao;Su, Lin;Xu, Zihang
非小细胞肺癌（NSCLC）占肺癌的85%以上，发病率和死亡率都很高。越来越多的研究表明，中药及其有效成分具有良好的抗肿瘤活性。然而，Thevebioside（THB）作为一种中药活性成分，其抗NSCLC的作用尚不清楚。在本研究中，据我们所知，这是第一次报告的基础上，我们以前的高通量筛选数据在NSCLC肿瘤抑制活性的潜在机制。我们进一步证明THB通过诱导细胞凋亡而不是细胞周期停滞来有效地抑制NSCLC细胞（A549和H460）的增殖。值得注意的是，通过体内和体外实验证明，THB处理后SRC-3显着下调，这依赖于遍在蛋白酶体介导的降解，随后抑制了IGF-1 R-PI 3 K-AKT信号通路并促进细胞凋亡。总体而言，THB通过泛素化抑制SRC 3介导的IGF-1 R-PI 3 K-AKT信号通路，诱导细胞凋亡，抑制NSCLC肿瘤生长，无论在体外还是体内，毒性都很小。
Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer with high incidence and mortality. Accumulating studies have shown that traditional Chinese medicine (TCM) and its active ingredients have good anti-tumor activity. However, the anti-tumor effect of Thevebioside (THB), an active ingredient from TCM, is still unknown in NSCLC. In this study, to our best knowledge, it was the first time to report the underlying mechanism of its tumor-suppressive activity in NSCLC based on our previous high-throughput screening data. We further demonstrated that THB effectively inhibited the proliferation of NSCLC cells (A549 and H460) by inducing cellular apoptosis rather than cell cycle arrest. Notably, it was demonstrated that SRC-3 was significantly down-regulated after THB treatment dependent on ubiquitin-proteasome-mediated degradation, which subsequently inhibited the IGF-1R-PI3K-AKT signaling pathway and promoted apoptosis via both in vivo and in vitro experiments. Collectively, THB exerted inhibitory effect on tumor growth of NSCLC through inhibiting SRC3 mediated IGF-1R-PI3K-AKT signaling by ubiquitination to induce cellular apoptosis with minimal toxicity no matter in vitro or vivo.