FORSKOLIN PROTECTS KERATINOCYTES FROM UVB-INDUCED APOPTOSIS AND INCREASES DNA REPAIR INDEPENDENT OF ITS EFFECTS ON MELANOGENESIS.

This study by researchers in the Laboratory of Cell Biology, National Cancer Institute (National Institutes of Health) demonstrated that MatTek’s melanocyte/keratinocyte-containing MelanoDerm in vitro human skin tissue equivalent can be used to investigate the ability of a topically applied compound to prevent UVB-induced DNA damage in keratinocytes independent of melanin production in melanocytes. Melanin pigments provide efficient protection against ultraviolet B (UVB) radiation but DNA repair also plays a key role in eliminating UV-induced damage and preventing the development of skin cancers. In this study, we demonstrate that forskolin (FSK), an agent that increases intracellular levels of cAMP, protects keratinocytes from UVB-induced apoptosis independently from the amount of melanin in the skin. We stained (melanin-containing) reconstructed skin tissues (MatTek’s MelanoDerm) with antibodies to the two major types of DNA damage resulting from UVB, cyclobutane pyrimidine dimers (CPDs) and 6,4-photoproducts (64PPs). Forskolin-treated and forskolin-untreated control skin tissues showed similar levels of CPD and 64PP 5 minutes after UVB exposure. However, after 6, 24, and 48 hours, the amounts of CPD and 64PP damage were significantly reduced in skin tissues pretreated with forskolin compared with untreated skin tissues, showing that forskolin is able to enhance the removal of UVB-induced DNA damage by facilitating DNA repair. These findings suggest new preventive approaches with topical formulations of forskolin or other bioactive agents that could be applied to the skin before sun exposure to increase its ability to repair DNA damage.

6,4-photoproducts, Apoptosis, Cyclobutane pyrimidine dimers, DNA Repair, DNA damage, EPI-100-NMM-113, Fontana-Masson staining, Forskolin, Hematoxylin-and-eosin staining, MEL-300-A, Melanin content, MelanoDerm, Sunburn cells, TUNEL, UVB-induced apoptosis

Forskolin (FSK), UVB