Possible Interaction: Linoleic Acid and Melatonin

“ Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumour LA uptake, 13‐HODE release, as well as significant reductions in tumour cAMP levels, DNA content and [3H]‐thymidine incorporation into DNA.”

“In rodent and human cancer xenografts of epithelial origin in vivo, melatonin suppresses the growth‐stimulatory effects of linoleic acid (LA) by blocking its uptake and metabolism to the mitogenic agent, 13‐hydroxyoctadecadienoic acid (13‐HODE).”

“This study tested the hypothesis that both acute and long‐term inhibitory effects of melatonin are exerted on LA transport and metabolism, and growth activity in tissue‐isolated human leiomyosarcoma (LMS), a rare, mesenchymally‐derived smooth muscle tissue sarcoma, via melatonin receptor‐mediated inhibition of signal transduction activity.”

“In hepatomas, through its activation of MT 1 and MT2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid.”

“ Melatonin and eicosapentaenoic and 10t,12c-conjugated linoleic acids suppress the growth-stimulating effects of linoleic acid (LA) and its metabolism to the mitogenic agent 13-(S)-hydroxyoctadecadienoic acid (13-(S)-HODE) in established rodent tumors and human cancer xenografts.”

“ Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts.”

“This group has elegantly shown that, in hepatoma cells, melatonin inhibits, via membrane receptor-mediated processes, the uptake and metabolism of fatty acids including linoleic acid (LA) and its conversion to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE).”

“By blocking tumor LA uptake, melatonin effectively blocks the production of 13-HODE and thus, markedly attenuates tumor growth.”

“The uptake of plasma linoleic acid and its metabolism to 13-HODE by rat hepatoma 7288CTC, which expresses both fatty acid transport protein and melatonin receptors, is inhibited by melatonin in a circadian-dependent manner.”

“The mechanism is suppression in the nighttime burst of melatonin , which has direct “oncostatic” properties and may alter the metabolism of linoleic and arachidonic acids leading to reduced 13-HODE, a proproliferative fatty acid metabolite.”

“Perfusion of tissue-isolated tumors in situ with melatonin (1 nM) rapidly and reversibly inhibited the uptake of plasma fatty acids (FAs), including LA , and its metabolism to 13-HODE.”

“The inhibition of these signal transduction events by melatonin culminates in the suppression of LA uptake, LA metabolism to the mitogenic signaling molecule 13-HODE, and cancer growth.”