Dalbinol, a rotenoid from Amorpha fruticosa L., exerts anti-proliferative activity by facilitating β-catenin degradation in hepatocellular carcinoma cells
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Xiaohui Zhu1,*, Xin Wu2,*, Jing Cheng3, Hongbo Liao2, Xiaoqing Di4, Lili Li1, Rong Li1, Yanfang Zhou1 and Xiangning Zhang1
1Department of Pathophysiology, Guangdong Medical University, Zhanjiang 524023, Guangdong, China
2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang 524023, Guangdong, China
3Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China
4Department of Pathology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
*These authors have contributed equally to this work
Yanfang Zhou, email: firstname.lastname@example.org
Xiangning Zhang, email: email@example.com
Keywords: dalbinol, hepatocellular carcinoma, Wnt/β-catenin, ubiquitin-proteasome degradation, cell proliferation
Received: November 24, 2016 Accepted: April 18, 2017 Published: May 10, 2017
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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