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Endocrinology. 2015 May;156(5):1630-6. doi: 10.1210/en.2014-1980. Epub 2015 Feb 13.

N1-Acetyl-5-Methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects.

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Departments of Pathology and Laboratory Medicine (T.-K.K., A.T.S.), Center for Cancer Research, and Pharmaceutical Sciences (Z.L., W.L.), University of Tennessee Health Science Center, Memphis, Tennessee 38163; Department of Dermatology (A.T.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294; and Department of Cellular and Structural Biology (R.J.R.), The University of Texas Health Science Center, San Antonio, Texas 78229.


Previously, we demonstrated that skin cells metabolize melatonin to 6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine and 5-methoxytryptamine. In this study, we determined that N1-acetyl-5-methoxykynuramine (AMK) is endogenously produced in the human epidermis from melatonin through the kynuric pathway. The epidermal content of AMK (average from 13 subjects) is 0.99 ± 0.21 ng/mg protein, being significantly higher in African Americans (1.50 ± 0.36 ng/mg protein) than in Caucasians (0.56 ± 0.09 ng/mg protein). It is especially high in young African Americans. The levels do not differ significantly between males and females. In vitro testing using HaCaT keratinocytes has shown that exogenously added melatonin is metabolized to AMK in a dose dependent manner with a Vmax = 388 pg/million cells and Km = 185 μM. AMK production is higher in melanized than in amelanotic melanoma cells. Testing of DNA incorporation shows that AMK has antiproliferative effects in HaCaT and SKMEL-188 cells (nonpigmented and pigmented). AMK also inhibits growth of normal melanocytes but has no significant effect on melanogenesis or cell morphology. These findings indicate that antiproliferative effects of AMK are not related to melanin pigmentation. In summary, we show for the first time that AMK is produced endogenously in the human epidermis, that its production is affected by melanin skin pigmentation, and that AMK exhibits antiproliferative effects in cultured keratinocytes and melanoma cells.

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