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HPV-18 transformed cells fail to arrest in G1 in response to quercetin treatment

R G Beniston1, M S Campo

  • 1Institute of Comparative Medicine, University of Glasgow, Garscube Estate G61 1QH, Glasgow, UK.

Virus Research
|March 15, 2005
PubMed

Insights

Quercetin, a compound in bracken fern, halts cell division in HPV-16 transformed cells but not HPV-18 transformed cells. This difference is due to quercetin up-regulating the HPV-18 long control region, maintaining viral protein expression.

Area of Science:

  • Oncology
  • Virology
  • Cell Biology

Background:

  • Quercetin, a mutagen in bracken fern, arrests primary human keratinocytes in G1 phase by increasing p27Kip1.
  • Human papillomavirus (HPV) infection is linked to esophageal cancer, with HPV-16 and HPV-18 being significant oncogenic types.

Purpose of the Study:

  • To investigate the effect of quercetin on cells transformed by the whole genome of HPV-16 and HPV-18.
  • To determine if quercetin induces G1 cell cycle arrest in HPV-18 transformed cells, similar to HPV-16 transformed cells.

Main Methods:

  • Treatment of HPV-16 and HPV-18 transformed keratinocytes with quercetin.
  • Analysis of cell cycle progression (G1 arrest) and expression of cyclin-dependent kinase inhibitor p27Kip1.
  • Investigation of the HPV-18 long control region (LCR) and quercetin responsive elements.

Main Results:

  • Quercetin induced G1 arrest and increased p27Kip1 in HPV-16 transformed cells, consistent with previous findings.
  • HPV-18 transformed cells did not exhibit G1 arrest upon quercetin treatment.
  • Quercetin up-regulated the HPV-18 LCR, maintaining high expression of viral oncoproteins, which prevented cell cycle arrest.

Conclusions:

  • The response to quercetin differs between HPV-16 and HPV-18 transformed cells.
  • Quercetin's effect on cell cycle arrest is mediated by differential regulation of viral LCRs.
  • A quercetin-responsive element in the HPV-18 LCR contributes to resistance to quercetin-induced cell cycle arrest.

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