Open AccessDalbinol, a rotenoid fromAmorpha fruticosa L., exerts anti-proliferative activity by facilitating β-catenin degradation in hepatocellular carcinoma cells
Author(s) -
Xiaohui Zhu,
Xin Wu,
Jing Cheng,
Hongbo Liao,
Di Xia,
Lili Li,
Rong Li,
Yanfang Zhou,
Xiangning Zhang
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.17766
Subject(s) - hepatocellular carcinoma , medicine , wnt signaling pathway , cancer research , china , oncology , biology , signal transduction , biochemistry , political science , law
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.