Polyunsaturated fatty acids, melatonin, and cancer prevention

Many nutritional, hormonal, and environmental factors affect carcinogenesis and growth of established tumors in rodents. In some cases, these factors may either enhance or attenuate the neoplastic process. Recent experiments performed in our laboratory using tissue-isolated rat hepatoma 7288CTC in v ivo or during perfusion in. situ have demonstrated new interactions among f our of these factors. Two agents, dietary linoleic acid (C18:2n6) and "ligh t at night," enhanced tumor growth, and two others, melatonin and n3 fatty acids, attenuated growth. Linoleic acid stimulated tumor growth because it is converted by hepatoma 7288CTC to the mitogen, 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin, the neurohormone synthesized and secreted at nig ht by the pineal gland, and dietary n3 fatty acids are potent antitumor age nts. Both inhibited tumor linoleic acid uptake and 13-HODE formation. Artif icial Light, specifically "light at night," increased tumor growth because it suppressed melatonin synthesis and enhanced 13-HODE formation. Melatonin and n3 fatty acids acted via similar or identical Gi protein-coupled signa l transduction pathways, except that melatonin receptors and putative n3 fa tty acid receptors were used. The results link the four factors in a common mechanism and provide new insights into the roles of dietary n6 and n3 pol yunsaturated fatty acid intake, "light at night," and melatonin in cancer p revention in humans. (C) 2001 Elsevier Science Inc. All rights reserved.