Integrity of a HPV11 infection cell model and identification of (-)-Epigallocatechin-3-gallate as a potential HPV11 inhibitor

Oncotarget. 2016 Jun 14;7(24):37092-37102. doi: 10.18632/oncotarget.9249.

Abstract

Background: Condyloma acuminatum (CA) is one of the most common sexually transmitted diseases and induced by low-risk human papillomaviruses (HPVs), mainly HPV type 6 and 11. Here, we report the identification of (-)-Epigallocatechin-3-gallate (EGCG) by an HPV11 infection cell model.

Results: The recombined HPV11.HaCaT cells had stable HPV 11 early genes expression. The introducing of HPV11 genome significantly increased the proliferation of HPV11.HaCaT cells, as well as the proportion of cells in S and G2/M phases. After treated with rhIFN-α 2a, IFN signaling pathway was activated in both HaCaT and HPV11.HaCaT cells, while HPV11 decreased the activation level. In addition, rhIFN-α 2a, could inhibit expression of HPV 11 E6 and E7 mRNA significantly (P<0.05). However, cell growth and cell cycle did not show statistical difference (P>0.05). Nevertheless, EGCG, a major active constituent in tea polyphenol, showed strong anti-HPV11 effect, which inhibited HPV11 E6 and E7 mRNA.

Methods: Gene transfection technique was used to introduce HPV11 genome into HaCaT cells, named HPV11.HaCaT cells. With the established cell model, we explore the anti-HPV11 effect of (-)-Epigallocatechin-3-gallate (EGCG) on cell growth, viability and affection on expression HPV11 E6 and E7 mRNA.

Conclusions: Our data collectively demonstrated that the recombinant HPV11.HaCaT cells were integral and practical to be a cell model to test anti-HPV11 agents and explore the interaction between HPV11 genes and host cells. And EGCG inhibits expression of HPV11 E6 and E7 mRNA in the recombinant HPV11.HaCaT cells.

Keywords: HPV11; IFN pathway; condyloma acuminatum; early genes; model.

MeSH terms

  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Culture Techniques / methods*
  • Cell Cycle / drug effects
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Cell Separation / methods
  • Condylomata Acuminata / drug therapy*
  • Condylomata Acuminata / immunology
  • Condylomata Acuminata / virology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression
  • Host-Pathogen Interactions / genetics
  • Human papillomavirus 11 / drug effects*
  • Human papillomavirus 11 / genetics
  • Humans
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology
  • Keratinocytes / immunology
  • Keratinocytes / virology*
  • Oncogene Proteins, Viral / metabolism
  • RNA, Messenger / metabolism
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction / immunology*
  • Transfection

Substances

  • E6 protein, Human papillomavirus type 11
  • E7 protein, human papillomavirus 11
  • IFNA2 protein, human
  • Interferon-alpha
  • Oncogene Proteins, Viral
  • RNA, Messenger
  • Recombinant Proteins
  • Catechin
  • epigallocatechin gallate