Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling

Overwhelming evidence that implicates aberrant activations of the canonical Wnt/β-catenin signaling pathway in oncogenesis and cancer progression has emerged in recent times. Accordingly, disruption of this signaling pathway offers an opportunity for effective cancer therapy. Despite various approaches to target components of the Wnt/β-catenin signaling pathway, safe and efficacious therapeutic agents have yet to be identified. As the search for novel small molecule inhibitors remains pressing and continues, natural products, which are traditionally excellent sources of lead compounds in the drug discovery and development process, are gaining prominence as effective antagonists of the signaling pathway. In this review, we will provide a comprehensive summary on the current use of natural compounds ranging from plant-derived polyphenols, anti-malarial artemisinins to several antimicrobial products as Wnt therapeutics and the development of more efficacious semi-synthetic analogues using these compounds as lead structures. We will also discuss pertinent issues that are limiting the rate of drug development based on these compounds and the chemical-biological significance across the diverse classes of natural compounds. The findings reviewed here should inspire and motivate more efforts to harness rich and diverse plant and other natural sources in the search for new leads as effective antagonists of the Wnt/β-catenin pathway.