DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells
复制标题
大黄丸靶向EGF信号抑制肝癌细胞增殖
DOI：
10.1371/journal.pone.0231466
复制
发表时间：
2020-04
期刊：
影响因子：
3.7
通讯作者：
Wang Hongyang
中科院分区：
文献类型：
--
作者：
Si Ha;Genna Ba;Zhuang Xiangjin;Wang Jing;Burenbatu B.;Feng Qiyu;Wang Hongyang
大黄丸是蒙古族治疗肝癌的传统中药。该药物的临床应用已被证明有助于控制肿瘤进展，延长生存期和提高生活质量。然而，该药物的潜在机制和副作用尚不清楚，这极大地限制了DHW的临床应用和进一步优化。在这项研究中，我们发现DHW通过调节上皮生长因子（EGF）信号通路来抑制肝癌细胞的增殖。黄连素和木香是DHW的主要活性成分。有趣的是，黄连素和木香的组合对抑制肝癌细胞的增殖具有显著的协同作用。黄连素和考司汀都不直接阻断EGFR磷酸化。小檗碱促进激活的EGFR的内吞作用，而考司汀增加EGFR的泛素化并减少EGFR再循环至细胞膜分布，从而抑制EGF信号传导。黄连素和Costunitol靶向调节EGF信号传导的两个不同步骤，这解释了DHW的协同抗癌作用。由于小檗碱和Costunitinib不直接靶向EGFR磷酸化，DHW可能是酪氨酸激酶抑制剂在癌症治疗中的补充药物。
DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy.
登录
查看更多内容
影响因子：
3.8
作者：
Sung-Min Moon;S. J. Yun;J. Kook;Heung-Joong Kim;Mi Suk Choi;B. Park;Su-Gwan Kim;Byung-Ock Kim;S. Lee;H. Ahn;H. Chun;Do Kyung Kim;C. Kim
通讯作者：
Sung-Min Moon;S. J. Yun;J. Kook;Heung-Joong Kim;Mi Suk Choi;B. Park;Su-Gwan Kim;Byung-Ock Kim;S. Lee;H. Ahn;H. Chun;Do Kyung Kim;C. Kim
影响因子：
5.6
作者：
Miyamoto Y;Suyama K;Baba H
通讯作者：
Baba H
研究EGF受体的内吞运输的方法。
影响因子：
--
作者：
Pinilla-Macua I;Sorkin A
通讯作者：
Sorkin A
分离β酸，其甲基酯和瓜伊安娜倍半萜与蛋白酪氨酸磷酸酶1B抑制活性，来自Saussurea Lappa C.B. Clarke的根。
DOI：
10.3390/molecules14010266
发表时间：
2009-01-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Choi JY;Na M;Hyun Hwang I;Ho Lee S;Young Bae E;Yeon Kim B;Seog Ahn J
通讯作者：
Seog Ahn J
影响因子：
--
作者：
A. Conte;S. Sigismund
通讯作者：
A. Conte;S. Sigismund