Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics

Abstract

The Wnt pathway has been recognized for its crucial role in human development and homeostasis, but its dysregulation has also been linked to several disorders, including cancer. Wnt signaling is crucial for the development and metastasis of several kinds of cancer. Moreover, members of the Wnt pathway have been proven to be effective biomarkers and promising cancer therapeutic targets. Abnormal stimulation of the Wnt signaling pathway has been linked to the initiation and advancement of cancer in both clinical research and in vitro investigations. A reduction in cancer incidence rate and an improvement in survival may result from targeting the Wnt/β-catenin pathway. As a result, blocking this pathway has been the focus of cancer research, and several candidates that can be targeted are currently being developed. Flavonoids derived from plants exhibit growth inhibitory, apoptotic, anti-angiogenic, and anti-migratory effects against various malignancies. Moreover, flavonoids influence different signaling pathways, including Wnt, to exert their anticancer effects. In this review, we comprehensively evaluate the influence of flavonoids on cancer development and metastasis by focusing on the Wnt/β-catenin signaling pathway, and we provide evidence of their impact on a number of molecular targets. Overall, this review will enhance our understanding of these natural products as Wnt pathway modulators.

Keywords: Wnt/β-catenin signaling; anticancer; flavonoids; natural product.

Figure 1

Wnt/β-catenin signaling pathway in tumor progression. The extracellular, cytoplasmic, and nuclear signaling events that constitute the Wnt/β-catenin signaling pathway can be therapeutically manipulated. β-catenin promotes the transcription of genes that are essential for CSCs, tumor metastasis, EMT, and tumor immunity after moving into the nucleus and interacting with TCF/LEF and a number of co-activators.

Figure 2

Effects of various flavonoids on the Wnt/β-catenin pathway. Flavonoids that modulate the Wnt cell signaling pathway by targeting Wnt ligands, receptors, intermediate signaling molecules, and downstream effector molecules in different cancer models are listed here.