Yu Wen-Kai, Xu Zhi-Yuan, Yuan Li, Mo Shaowei, Xu Beihua, Cheng Xiang-Dong, Qin Jiang-Jiang
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Front Pharmacol. 2020 Jun 30;11:984. doi: 10.3389/fphar.2020.00984. eCollection 2020.
The mutations and deregulation of Wnt signaling pathway occur commonly in human cancer and cause the aberrant activation of β-catenin and β-catenin-dependent transcription, thus contributing to cancer development and progression. Therefore, β-catenin has been demonstrated as a promising target for cancer prevention and therapy. Many natural products have been characterized as inhibitors of the β-catenin signaling through down-regulating β-catenin expression, modulating its phosphorylation, promoting its ubiquitination and proteasomal degradation, inhibiting its nuclear translocation, or other molecular mechanisms. These natural product inhibitors have shown preventive and therapeutic efficacy in various cancer models and . In the present review, we comprehensively discuss the natural product β-catenin inhibitors, their and anticancer activities, and underlying molecular mechanisms. We also discuss the current β-catenin-targeting strategies and other potential strategies that may be examined for identifying new β-catenin inhibitors as cancer preventive and therapeutic drugs.
Wnt信号通路的突变和失调在人类癌症中普遍存在,会导致β-连环蛋白及β-连环蛋白依赖性转录的异常激活,从而促进癌症的发生和发展。因此,β-连环蛋白已被证明是癌症预防和治疗的一个有前景的靶点。许多天然产物已被鉴定为β-连环蛋白信号的抑制剂,它们通过下调β-连环蛋白表达、调节其磷酸化、促进其泛素化和蛋白酶体降解、抑制其核转位或其他分子机制来发挥作用。这些天然产物抑制剂在各种癌症模型中已显示出预防和治疗效果。在本综述中,我们全面讨论了天然产物β-连环蛋白抑制剂、它们的抗癌活性及其潜在分子机制。我们还讨论了当前针对β-连环蛋白的策略以及其他可能用于鉴定新型β-连环蛋白抑制剂作为癌症预防和治疗药物的潜在策略。