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

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.