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Published on: January 20, 2016
Natural small molecule compounds targeting Wnt signaling pathway inhibit HPV infection
Tao Zhang1, Ze Wang2, Munawaer Muaibati2
1Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518057, China.
Background:
High-risk human papillomavirus (HPV) infection is a major risk factor of HPV-related tumors, especially cervical cancer. To date, there is no specific drug for the treatment of HPV infection.
Purpose:
To explore the role of canonical Wnt signaling pathway in HPV16 infection and to screen inhibitors against HPV16 infection from natural small molecule compounds targeting the canonicalWnt pathway.
Methods:
Wnt pathway inhibitor IWP-2 and FH535 were used to inhibit Wnt/β-catenin signaling pathway. HPV16-GFP pseudovirus infectivity were analyzed by fluorescence microscopy and fluorescence activated cell sorting. A small molecule screening of a total of CFDA-approved 29 natural compounds targeting the Wnt pathway was performed.
Results:
Wnt signaling pathway inhibitor suppressed HPV16-GFP pseudovirus infection in HaCat cells. Natural small molecule compounds screening identified 6-Gingerol, gossypol, tanshinone II2A, and EGCG as inhibitors of HPV16-GFP pseudovirus infection.
Conclusion:
Wnt signaling pathway is involved in the process of HPV infection of host cells. 6-Gingerol, gossypol, tanshinone II2A, and EGCG inhibited HPV16-GFP pseudovirus infection and suppressed Wnt/β-catenin pathway in HaCat cells.
Insights
High-risk human papillomavirus (HPV) infection, a cause of cervical cancer, may be treatable. Researchers found that targeting the Wnt signaling pathway with natural compounds like 6-Gingerol inhibited HPV infection.
Area of Science:
- Virology and molecular biology
- Cancer research
- Drug discovery
Background:
- High-risk human papillomavirus (HPV) infection is a significant risk factor for HPV-related cancers, notably cervical cancer.
- Currently, no specific antiviral drugs exist for treating HPV infections.
Purpose of the Study:
- To investigate the involvement of the canonical Wnt signaling pathway in HPV16 infection.
- To identify natural small molecule compounds that inhibit HPV16 infection by targeting the Wnt pathway.
Main Methods:
- Inhibition of the Wnt/β-catenin signaling pathway using specific inhibitors (IWP-2, FH535).
- Assessment of HPV16-GFP pseudovirus infectivity via fluorescence microscopy and flow cytometry.
- Screening of 29 FDA-approved natural compounds targeting the Wnt pathway.
Main Results:
- Wnt signaling pathway inhibitors demonstrated suppression of HPV16-GFP pseudovirus infection in HaCat cells.
- The screening identified 6-Gingerol, gossypol, tanshinone II2A, and EGCG as effective inhibitors of HPV16-GFP pseudovirus infection.
- These compounds also suppressed the Wnt/β-catenin pathway in HaCat cells.
Conclusions:
- The canonical Wnt signaling pathway plays a role in host cell infection by HPV.
- Natural compounds 6-Gingerol, gossypol, tanshinone II2A, and EGCG show potential as therapeutic agents against HPV infection by inhibiting the Wnt/β-catenin pathway.
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