Abstract Number: 5671 A topical niacin prodrug for skin cancer prevention Hyuntae Kim, Moonsun Kim, Jaber Qasem, Donna Coyle, Myron Jacobson, Elaine L. Jacobson, Arizona Cancer Center, Tucson, AZ; Niadyne, Inc, Tucson, AZ. Niacin (nicotinic acid) has been shown to function as both a micronutrient and as a drug. Animal studies demonstrate that high-dose niacin supplementation is effective in preventing both UV-induced immune suppression and UV-induced skin cancer. Two targets have been identified that can account for the observed effects of niacin on UV-induced skin cancer and immune suppression; poly(ADP-ribose) polymerase-1 (PARP-1) whose activity is enhanced by niacin due to increased substrate availability and the protective cytokine, leptin and its signaling pathways, which are stimulated by niacin. PARP-1 functions in the synthesis of chromatin-associated polymers of ADP-ribose that function in cellular recovery from DNA damage and maintenance of genomic stability. The activation of PARP-1 by DNA strand breaks leads to complex signaling pathways that can enhance cell survival, result in cell death by apoptosis, or cause energy loss that leads to necrosis. A second target for the effects of niacin on skin cancer incidence and immune suppression has been identified by our recent discovery that niacin causes increases in plasma leptin. The finding that niacin modulates leptin metabolism has strong implications with regard to the known roles of leptin in skin barrier function and immune modulation. Our preclinical studies show that niacin must be used in therapeutic doses to inhibit skin cancer. The most common side effect of therapeutic doses of oral niacin is flushing and hepatotoxicity. Therefore, in order to circumvent these problems, a topical prodrug for delivery of niacin to skin cells has been developed. We show here that topical niacin prodrugs can elevate the NAD content of skin at the site of application without vasodilation, and increase plasma leptin in mice. Topcal niacin prodrugs appear to be a promising skin cancer prevention agent both as a micronutrient and a drug. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.