Ultraviolet-B (UVB) radiation plays a pivotal role in non-melanoma human skin cancers (NMSCs) by inducing cellular DNA damage, mutations and immunosuppression. Decades of research has demonstrated silibinin efficacy against UVB-induced skin carcinogenesis by regulating different molecular pathways in various cell lines and animal models; however, the role of silibinin in regulating interleukin-12 (IL-12), an immunomodulatory cytokine with the capacity to reduce UVB-induced DNA damage and apoptosis, has not been studied. Here, we report that UVB irradiation caused a dose- and time-dependent caspase 3 and PARP cleavage as well as apoptosis in JB6 cells. Addition of recombinant IL-12 or silibinin immediately after UVB significantly protected UVB-induced apoptosis in JB6 cells, and antibody-mediated blocking of IL-12 activity compromised the protective effect of both IL-12 and silibinin. In addition, both silibinin and IL-12 accelerated the repair of UVB-caused cyclobutane-pyrimidine dimers (CPDs) in JB6 cells. Additional studies confirmed that indeed silibinin causes a significant increase in IL-12 levels in UVB-irradiated JB6 cells as well as in the SKH-1 hairless mouse epidermis, and that similar to in vitro findings, silibinin topical application immediately after UVB exposure causes a very strong protection against UVB-induced TUNEL positive cells in epidermis possibly through a significantly accelerated repair of UVB-caused CPDs in skin epidermis. Together, these findings for the first time identify an important insight regarding the pharmacological mechanism wherein silibinin induces endogenous IL-12 in its efficacy against UVB-caused skin damages. Considering the fact that millions of people get constantly exposed to solar UVB radiation and live with persistent UVB-induced DNA lesions, the post-damage use of silibinin as an inducer of endogenous IL-12 in UVB-damaged human skin for the rapid repair of DNA damage could be a more practical and translational approach in reducing sunlight-caused damages in human skin which eventually lead to NMSCs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1592. doi:1538-7445.AM2012-1592