Cidofovir induces an increase in levels of low-risk and high-risk HPV E6

Head Neck. 2009 Jul;31(7):893-901. doi: 10.1002/hed.21043.

Abstract

Background: Cidofovir is a nucleoside analogue that is used off-license to treat recurrent respiratory papillomatosis (RRP) caused by HPV6/11. However, the effect of this drug upon low-risk HPV 6/11 gene expression is unknown.

Methods: The expression of E6 was evaluated by RT-PCR in HPV-ve C33A cervical carcinoma cells stably transfected with both low- and high-risk HPV E6 cDNA's and in SiHa (HPV16+ve) cervical carcinoma cells after treatment with 2 doses and durations of exposure to cidofovir.

Results: Compared to the vector only transcript, E6 RNA levels showed an 8-fold increase in low-risk and 20-fold increase in high-risk E6-expressing cells. High-risk E6 protein levels were also detected by Western blot in cidofovir-treated C33A Type16 E6-transfected cells.

Conclusion: These data may indicate a potential rationale for increased risk of genetic instability and thus transformation due to drug-induced increase in the level of E6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Culture Techniques
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Female
  • Human papillomavirus 6 / drug effects*
  • Human papillomavirus 6 / genetics
  • Human papillomavirus 6 / metabolism
  • Humans
  • Oncogene Proteins, Viral / drug effects*
  • Oncogene Proteins, Viral / metabolism*
  • Organophosphonates / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • RNA, Viral / drug effects
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*

Substances

  • Antiviral Agents
  • E6 protein, Human papillomavirus type 6
  • Oncogene Proteins, Viral
  • Organophosphonates
  • RNA, Messenger
  • RNA, Viral
  • Cytosine
  • Cidofovir