Abstract Number: 3203 Dietary melatonin inhibits tumor growth via melatonin receptor-mediated suppression of tumor Linoleic Acid (LA) uptake and metabolism David E. Blask, Robert T. Dauchy, Leonard A. Sauer, Jean A. Krause, Bassett Research Institute, Cooperstown, NY. The pineal gland hormone melatonin has significant anticancer growth activity. Daily, late afternoon injections of pharmacological doses of melatonin inhibit the growth of rat hepatoma 7288CTC by blocking the tumor uptake of LA and epidermal growth factor (EGF)-stimulated metabolism of LA to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). This occurs via a melatonin Gi protein receptor-mediated inhibition of cAMP formation. Melatonin is also present in significant amounts in a variety of edible plants. Millions of people take over-the-counter melatonin supplements as a sleep aid and/or treatment for jet lag. We tested whether the dietary intake of melatonin, in quantities present in edible plants and nutritional supplements, would also inhibit hepatoma 7288CTC growth. Adult male Buffalo rats maintained on a 12L:12D light/dark cycle had access to a semi-purified diet containing 5% corn oil ad libitum. Melatonin was added to the diet such that subgroups of rats ingested different amounts of melatonin (0, 0.05, 0.5 or 5 ėg/day) beginning 1 week prior to hepatoma implantation and continuing for several weeks until the end of the tumor growth study. There was a significant (p < 0.05) dose-dependent inhibition of tumor growth in animals ingesting melatonin with no inhibition at 0.05 ėg/day and maximal growth inhibition at 5 ėg/day. Arteriovenous difference measurements across tumors in vivo revealed a similar, significant (p < 0.05) dose-dependent suppression of tumor LA uptake and 13-HODE formation. There was also a significant (p < 0.05) dose-related increase in the intratumoral levels of melatonin. The suppressive effects of dietary melatonin on tumor growth, LA uptake, 13-HODE formation as well as the intratumoral increase in melatonin levels were totally blocked by the co-ingestion of the melatonin receptor antagonist S-20928. These results indicate that melatonin supplied in the diet, in amounts similar to those found in melatonin supplements and some edible plants, inhibits the growth of hepatoma 7288CTC. Both the melatonin-induced inhibition of tumor LA uptake and 13-HODE formation, and the tumor uptake and retention of melatonin itself are mediated by melatonin receptor-regulated signal transduction events. Supported by NIH CA76197 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.