Aberrant canonical Wnt signaling: Phytochemical based modulation

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology
• Pathology

Background:

• The Wnt signaling pathway is crucial for embryonic development and its dysregulation is implicated in diseases such as cancer, osteoporosis, and Alzheimer's.
• Phytochemicals, including flavonoids, glycosides, and polyphenols, have demonstrated the ability to directly interact with Wnt signaling pathway components.

Purpose of the Study:

• To comprehensively review phytochemicals that target key players of the Wnt signaling pathway in cancer, osteoporosis, and Alzheimer's disease.
• To elucidate the pharmacological mechanisms by which phytochemicals alleviate disease symptoms through Wnt signaling modulation.

Main Methods:

• Systematic literature search of preclinical rodent and in vitro cell line studies from 2005-2019.
• Databases searched include Scopus, Web of Science, and PubMed using keywords: Canonical Wnt signaling pathway, Cancer, Alzheimer's disease, Osteoporosis, Phytochemicals.
• Focus on studies identifying target-specific modulation of Wnt signaling by phytochemicals.

Main Results:

• Approximately 30 phytochemicals were identified to modulate Wnt signaling by affecting targets like Axin, β-catenin, GSK-3β, AKT, and Wif-1.
• Wnt signaling downregulation is observed in cancers (e.g., colorectal, breast) due to mutations; phytochemicals show potential in alleviating cancer.
• Wnt signaling upregulation is associated with osteoporosis and Alzheimer's disease.

Conclusions:

• Phytochemicals offer potential therapeutic strategies by targeting Wnt signaling markers, with the ability to either activate or inhibit the pathway.
• Challenges in precise Wnt signaling targeting and the risks of pathway dysregulation are discussed.
• The Wnt signaling pathway presents a promising therapeutic target for various diseases.