Abstract
Ultraviolet B (UVB), a complete environmental carcinogen, is known to cause oxidative stress and inflammation that are associated with skin cancer. Antioxidative and anti-inflammatory phytochemicals have been shown to protect against UVB-induced skin injury and carcinogenesis. Rutin is a flavonol glycoside which is composed of quercetin and rutinose and abundant in onions, apples, tea and red wine. In the present study, topical application of rutin (1 or 5 \#956;mol), onto the dorsal skin of female HR-1 hairless mice 30 min prior to UVB irradiation (180 mJ/cm2) diminished the formation of 4-hydroxynonenal at 24 h, a biochemical hallmark of lipid peroxidation. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme involved in prostaglandin biosynthesis, has been implicated in various inflammatory disorders and tumor promotion. Pretreatment with rutin significantly inhibited UVB-induced COX-2 expression at 6 h in mouse skin as determined by immunoblot and immunohistochemical analyses. Notably, there was effective inhibition by rutin of UVB-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK), but not that of extracellular signal-regulated protein kinase (ERK) in HR-1 hairless mouse skin. Signal transducer and activator of transcription-3 (Stat3) protein belongs to a family of latent transcription factors and plays a crucial role in skin carcinogenesis. Topically applied rutin significantly attenuated UVB-induced phosphorylation of Stat3. Activator protein-1 (AP-1) is a key regulator of UVB-induced COX-2 expression. The DNA binding activity of AP-1 was also markedly decreased following pretreatment with rutin in UVB-irradiated mouse skin. These findings suggest the chemopreventive potential of rutin in protecting against skin photodamage and photocarcinogenesis.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3921.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO
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