Abstract 4644: Curcumin C3 ® prevents ultraviolet B radiation-induced acute damage in JB6 keratinocytes and mouse skin via FGF-2/mTOR/NF-KB pathway

Abstract

Abstract Background and Significance: Aggressive Cutaneous Squamous cell carcinoma (CSCC) of the face has become the second most common type of skin cancer in the USA due to ultraviolet B (UVB) exposure in tanning booths and sun exposure of our military personnel. UVB is a carcinogen and our previous studies established oral administration of Curcumin C3 complex (C3), a standardized preparation of three curcumonoids - Curcumin (76.07%), Demethoxycurcumin (20.28%) and Bisdemethoxycurcumin (3.63%), 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 in promotion sensitive JB6 skin keratinocytes and SKH-1 hairless mouse epidermis on the early 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 UVB-induced early molecular signaling 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. In vitro, C3®blocked UVB-dependent FGF-2 induction and proliferation of cultured keratinocytes via down regulation of nuclear factor kappa B (NF-KB) and Mammalian target of rapamycin (mTOR) signaling pathways. Conclusion: Our findings suggest C3® has the ability to protect mice from UVB-induced acute damage. Further the photo-preventive effects of C3® are mediated, at least in part, via modulation of FGF-2/mTOR/NF-KB signaling. Citation Format: Alok R. Khandelwal, Arun Anandharaj, Ekshyyan Oleksandr, Tara Moore-Medlin, Abreo Fleurette, Cherie-Ann O. Nathan. Curcumin C3 ® prevents ultraviolet B radiation-induced acute damage in JB6 keratinocytes and mouse skin via FGF-2/mTOR/NF-KB pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4644. doi:10.1158/1538-7445.AM2015-4644