Abstract B47: Curcumin C3 ® prevents ultraviolet B radiation-induced epidermal damage in JB6 cells and mouse skin via a Fibroblast growth factor-2-dependent manner

Abstract

Abstract Background and Significance: Non-melanoma skin cancer (NMSC) is the most common skin cancer in the U.S., with over a million new cases anticipated annually. Cutaneous squamous cell carcinoma (SCC) is a more aggressive form of NMSC. Chronic exposure to solar ultraviolet (UVB) is the major etiologic factor causing skin cell damage, photoaging and malignant transformation leading to SCC. UVB is a carcinogen and our previous studies established oral administration of Curcumin C3 complex (C3), a natural occurring polyphenol compound mixture, delayed UVB-induced tumor onset and multiplicity, but not tumor progression. Accordingly, we sort to determine the preventative efficacy of C3® against UVB-induced photodamage using JB6 cells and SKH-1 hairless mouse epidermis on the earlier neoplastic events in the development of UVB-induced skin carcinogenesis. Methods: SKH-1 mice were either administered vehicle or C3 (100mg/kg/b.w) complex orally for 14 days followed by a single exposure to UVB radiation (180mj/cm2). Mice were euthanized 24 hours after UVB exposure and skin tissues and serum were collected. For in vitro studies, promoter–sensitive JB6 mouse epithelial cells were pre-treated with C3® for 2 h and the effects on UV-induced early molecular events were assessed. Results: C3® attenuated UVB-induced epidermal hyperplasia and significantly decreased epidermal and plasma levels of fibroblast growth factor-2 (FGF-2); an important mitogen implicated in proliferation and differentiation of skin keratinocytes. Interestingly, the effects of C3® complex on FGF-2 levels were accompanied with a significant reduction in UVB-induced Nuclear factor KappaB (NF-KB) activation; an important nuclear transcription factor for tumor promotion. Further, the decrease in NF-KB was associated with an inhibition of BCL2 expression to induce apoptosis. In vitro, pretreatment of JB6 cells with C3® significantly decreased UVB-induced proliferation with a corresponding decrease in FGF-2 mRNA and protein levels. Further, C3 complex inhibited NF-KB phosphorylation and increased Bax expression leading to cell apoptosis. Conclusion: Our findings underscore the importance of curcumin (C3) in preventing UVB-induced skin cancer. It provides new insight into curcumin's role through FGF-2 in modulating the pathogenesis of photo carcinogenesis. Citation Format: Alok R. Khandelwal, Arun Anandharaj, Oleksandr Ekshyyan, Lauren D. Saucier, Tara N. Moore-Medlin, Fleurette Abreo, Cherie-Ann O. Nathan. Curcumin C3 ® prevents ultraviolet B radiation-induced epidermal damage in JB6 cells and mouse skin via a Fibroblast growth factor-2-dependent manner. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B47.