Natural small molecule compounds targeting Wnt signaling pathway inhibit HPV infection

  • Microb Pathog. 2024 Nov:196:106960. doi: 10.1016/j.micpath.2024.106960.
Tao Zhang  1 ,  Ze Wang  2 ,  Munawaer Muaibati  2 ,  Fanwei Huang  2 ,  Kexin Li  2 ,  Abuduyilimu Abasi  2 ,  Qing Tong  2 ,  Dan Wang  3 ,  Lei Jin  4 ,  Xiaoyuan Huang  2 ,  Liang Zhuang  5
Affiliations
  • 1. Reproductive 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.
  • 2. Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, China.
  • 3. Department of Ophthalmology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4. Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, China.
  • 5. Department of Oncology, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, China. Electronic address: [email protected].
PMID: 39313132 DOI: 10.1016/j.micpath.2024.106960
Abstract

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.

Keywords
6-Gingerol; EGCG; Gossypol; Human papillomavirus; Tanshinone II2A; Wnt/β-catenin signaling pathway.
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