The recent update and advancements of natural products in targeting the Wnt/β-Catenin pathway for cancer prevention and therapeutics.

Abstract

The Wnt/β-Catenin pathway (Wnt/β-CatP) is implicated in accelerating carcinogenesis and cancer progression, contributing to increased morbidity and treatment resistance. Even though it holds promise as a focus for cancer treatment, its intricate nature and diverse physiological effects pose significant challenges. Recent years have witnessed significant advancements in this domain, with numerous natural products demonstrating promising preclinical anti-tumor effects and identified as inhibitors of the Wnt/β-CatP through various upstream and downstream mechanisms. This study provides a comprehensive overview of the current landscape of Wnt/β-Cat-targeted cancer therapy, examining the impact of natural products on Wnt/β-Cat signaling in both cancer prevention and therapeutic contexts. A comprehensive search was conducted on scientific databases like SciFinder, PubMed, and Google Scholar to retrieve relevant literature on Wnt-signaling, natural products, β-Catenin (β-Cat), and cancer from 2020 to January 2024. As per the analysis of the relevant reference within the specified period, it has been noted that a total of 58 phytoconstituents, predominantly phenolics, followed by triterpenoids and several other classes, along with a limited number of plant extracts, have exhibited activity targeting the Wnt/β-CatP. Most β-Cat regulating modulators restrict cancer cell development by suppressing β-Cat expression, facilitating proteasomal degradation, and inhibiting nuclear translocation. Multiple approaches have been devised to block the activity of β-Cat in cancer therapy, a key factor in cancer progression, leading to the discovery of various Wnt/β-CatP regulators. However, their exploration remains limited, necessitating further research using clinical models for potential clinical use in cancer prevention and therapeutics.