Curcumin and Rutin Down-regulate Cyclooxygenase-2 and Reduce Tumor-associated Inflammation in HPV16-Transgenic Mice

Anticancer Res. 2018 Mar;38(3):1461-1466. doi: 10.21873/anticanres.12371.

Abstract

Aim: Cyclo-oxygenase-2 (COX2) plays a prominent role in carcinogenesis. This study addresses the effects of two nutraceutical compounds on the expression of COX2 and tumor-associated inflammation in human papillomavirus type 16 (HPV16)-transgenic mice.

Materials and methods: Six-week-old FVB/n mice were supplemented with rutin or curcumin for 24 weeks: HPV16-/- no treatment, n=12; HPV16+/- no treatment, n=13; HPV16+/- rutin, n=12; HPV16+/- curcumin, n=13. HPV16-induced skin lesions and their inflammatory infiltrates were studied histologically. COX2 expression was assessed immunohistochemically.

Results: Rutin reduced COX2 expression in the dermis (immunostaining score 7.83 versus 11.25 in untreated HPV16-transgenic mice) and epidermis (4.5 versus 10.0). Curcumin led to dermal and epidermal scores of 10.5 and 4.5. Both compounds reduced leukocytic infiltration, but neither prevented epidermal dysplasia.

Conclusion: COX2 expression in HPV16-induced lesions may be modulated by nutraceuticals, reducing tumor-associated inflammation. However, this was not sufficient to block carcinogenesis, calling for additional studies focused on combination therapies.

Keywords: HPV; diet; inflammation; mouse model; nutraceutic.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Curcumin / pharmacology*
  • Cyclooxygenase 2 / metabolism*
  • Disease Progression
  • Down-Regulation / drug effects
  • Female
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / physiology
  • Humans
  • Inflammation / complications
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Leukocytes / drug effects
  • Leukocytes / pathology
  • Mice, Transgenic
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / virology
  • Rutin / pharmacology*
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / complications
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / prevention & control*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Rutin
  • Cyclooxygenase 2
  • Curcumin