Abstract

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 in vitro and in vivo. In the present review, we comprehensively discuss the natural product β-catenin inhibitors, their in vitro and in vivo 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.

Highlights

  • Reviewed by: Wen Zhou, Guangzhou University of Chinese Medicine, China Xin Luan, Shanghai University of Traditional Chinese Medicine, China

  • Considering the critical role of b-catenin signaling in cancer development and progression, several targeting strategies have been developed to inhibit b-catenin, resulting in the identification of various types of b-catenin inhibitors (Krishnamurthy and Kurzrock, 2018; Qin et al, 2018b)

  • Several natural products have been shown to inhibit the b-catenin signaling via different molecular mechanisms, including, but not limited to, 1) down-regulating b-catenin expression, 2) modulating b-catenin phosphorylation and inducing its inactivation, 3) promoting bcatenin protein ubiquitination and proteasomal degradation, 4) inhibiting b-catenin nuclear translocation, and 5) other

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Summary

Introduction

Reviewed by: Wen Zhou, Guangzhou University of Chinese Medicine, China Xin Luan, Shanghai University of Traditional Chinese Medicine, China. Bi et al have found that ginsenoside 20(S)-25-OCH3-PPD inhibits the viability and induces apoptosis in colon and lung cancer cells by downregulating the protein expression of b-catenin and its targets CDK4, cyclin D1, c-Myc, and TCF4 (Bi et al, 2009).

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