Dalbinol, a rotenoid from Amorpha fruticosa L., exerts anti-proliferative activity by facilitating β-catenin degradation in hepatocellular carcinoma cells.
Dalbinol, a rotenoid from Amorpha fruticosa L., exerts anti-proliferative activity by facilitating β-catenin degradation in hepatocellular carcinoma cells.
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Dalbinol 是一种来自 Amorpha fruticosa L. 的鱼藤素，通过促进肝细胞癌细胞中的 β-catenin 降解发挥抗增殖活性
DOI：
10.18632/oncotarget.17766
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Zhu X;Wu X;Cheng J;Liao H;Di X;Li L;Li R;Zhou Y;Zhang X
肝细胞癌（HCC）是一种高度恶性的肿瘤，恶性增殖是导致治疗失败的主要原因。Wnt/β-catenin信号传导的异常与HCC的发展相关。尽管在过去的十年中，分子靶向治疗的出现改善了总生存率，但这些治疗并不是对所有不同病因的患者都有效。因此，存在对用于HCC的新型化疗剂的需求。为此，我们构建了紫穗槐天然化合物库，从紫穗槐种子中筛选出一种名为dalbinol的鱼藤素类化合物。结果表明，dalbinol对HepG 2、HepG 2/ADM和Huh 7细胞的生长有明显的抑制作用，且呈浓度依赖性。药理学实验也表明，在体外，dalbinol抑制这些肝癌细胞系的生长和诱导凋亡。此外，我们发现dalbinol促进β-catenin降解，这是通过泛素-蛋白酶体途径介导的。总之，我们的研究结果表明，dalbinol抑制肝癌细胞的生长，促进β-连环蛋白降解通过泛素-蛋白酶体途径。因此，我们认为，dalbinol将是一个有前途的药物治疗肝癌亚型异常Wnt/β-连环蛋白途径激活。
Hepatocellular carcinoma (HCC) is a highly malignant tumor, and the main cause of treatment failure is malignant proliferation. Aberrations in Wnt/β-catenin signaling are associated with HCC development. Despite the improvements in overall survival made over the past decade from the advent of molecularly targeted therapies, these treatments do not have efficacy in all patients with different pathogeneses. Therefore, there is a demand for novel chemotherapeutic agents for HCC. To this end, we built a natural compound library and screened out a rotenoid named dalbinol from the seeds of Amorpha fruticosa L. Our data demonstrated that dalbinol inhibited the growth of HepG2, HepG2/ADM and Huh7 cells in a concentration-dependent manner. Pharmacological experiments also showed that dalbinol suppressed growth and induced apoptosis in these HCC cell lines in vitro. Furthermore, we found that dalbinol promoted β-catenin degradation, which was mediated by the ubiquitin-proteasome pathway. To summarize, our results illustrate that dalbinol inhibited HCC cell growth by facilitating β-catenin degradation through the ubiquitin-proteasome pathway. Hence, we propose that dalbinol will be a promising agent for the treatment of HCC subtypes with aberrant Wnt/β-catenin pathway activation.
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影响因子：
4.2
作者：
Hoshida Y;Toffanin S;Lachenmayer A;Villanueva A;Minguez B;Llovet JM
通讯作者：
Llovet JM
DOI：
10.1073/pnas.92.7.3046
发表时间：
1995-03-28
影响因子：
11.1
作者：
MUNEMITSU, S;ALBERT, I;POLAKIS, P
通讯作者：
POLAKIS, P
影响因子：
3.3
作者：
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Mehta, Rajendra G.
影响因子：
51.1
作者：
Faivre, Sandrine;Raymond, Eric;Cheng, Ann Lii
通讯作者：
Cheng, Ann Lii
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi