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Updated: Dec 18, 2025
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Aberrant canonical Wnt signaling: Phytochemical based modulation
Suman Manandhar1, Shama Prasada Kabekkodu2, K Sreedhara Ranganath Pai1
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, India.
Background:
Wnt signaling pathway plays a major role during development like gastrulation, axis formation, organ development and organization of body plan development. Wnt signaling aberration has been linked with various disease conditions like osteoporosis, colon cancer, hair follicle tumor, Leukemia, and Alzheimer's disease. Phytochemicals like flavonoid, glycosides, polyphenols, have been reported to directly target the markers of Wnt signaling in different disease models.
Purpose:
The study deals in detail about the different phytochemical targeting key players of Wnt signaling pathway in diseases like Cancer, Osteoporosis, and Alzheimer's disease. We have focused on the Pharmacological basis of disease alleviation by phytochemical specifically targeting the Wnt signaling markers in this study.
Methods:
The study focused on the published articles from the preclinical rodent and invitro cell line studies related to Wnt signaling and Phytochemicals related to Cancer, Alzheimer's and Osteoporosis. The electronic databases Scopus, Web of Science and Pubmed database were used for the systematic search of literatures from 2005 up to 2019 using keywords Canonical Wnt signaling pathway, Cancer, Alzheimer's disease, Osteoporosis, Phytochemicals. The focus was to identify the target specific modulation of Wnt signaling mediated by phytochemicals.
Results:
Approximately 30 phytochemicals of different class have been identified to modulate Wnt signaling pathway acting through Axin, β-catenin translocation, GSK-3β, AKT, Wif-1 in various experimental studies. The down regulation of Wnt signaling is observed in Cancer mostly colorectal cancer, breast cancer mediated through mutations in APC and Axin genes. Different class of Phytochemicals such as flavonoid, glycosides, polyphenol, alkaloids etc. have been found to target Wnt signaling markers and alleviate Cancer. Similarly, Up regulation of Wnt signaling has been reported in Osteoporosis and neurodegenerative disease like Alzheimer's disease.
Conclusion:
This review highlights the possibility of the Phytochemicals to target Wnt markers and its potential to either activate or deactivate the Wnt signaling pathway. It also describes the challenges in proper targeting of Wnt signaling and the potential risk and consequences of either up regulation or down regulation of the signaling pathway. This article highlights the possibility of Wnt signaling pathway as a therapeutic option in different diseases.
Insights
Phytochemicals can target Wnt signaling pathways to treat diseases like cancer, osteoporosis, and Alzheimer's. This review explores how these natural compounds modulate Wnt signaling for therapeutic benefits.
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.
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