N<sup>1</sup>-acetyl-5-methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects

Tae Kang Kim, Zongtao Lin, Wei Li, Russel J Reiter, Andrzej T. Slominski

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Previously, we demonstrated that skin cells metabolize melatonin to 6-hydroxymelatonin, N<sup>1</sup>-acetyl- N<sup>2</sup>-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 melatoninthroughthe kynuricpathway.Theepidermal content ofAMK(averagefrom13subjects) 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 V<inf>max</inf> = 388 pg/million cells and K<inf>m</inf> = 185 μM. AMK production is higher in melanized than in amelanoticmelanomacells. Testing ofDNAincorporationshowsthatAMKhasantiproliferative effects in HaCaT and SKMEL-188 cells (nonpigmented and pigmented). AMK also inhibits growth of normal melanocytesbuthasnosignificant effectonmelanogenesisor cellmorphology.Thesefindings 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.

Original languageEnglish (US)
Pages (from-to)1630-1636
Number of pages7
JournalEndocrinology
Volume156
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Fingerprint

Epidermis
Melanins
Melatonin
Keratinocytes
African Americans
5-Methoxytryptamine
Skin Pigmentation
Proteins
Pigmentation
Melanoma
Skin
Growth

ASJC Scopus subject areas

  • Endocrinology

Cite this

N<sup>1</sup>-acetyl-5-methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects. / Kim, Tae Kang; Lin, Zongtao; Li, Wei; Reiter, Russel J; Slominski, Andrzej T.

In: Endocrinology, Vol. 156, No. 5, 01.05.2015, p. 1630-1636.

Research output: Contribution to journalArticle

Kim, Tae Kang ; Lin, Zongtao ; Li, Wei ; Reiter, Russel J ; Slominski, Andrzej T. / N<sup>1</sup>-acetyl-5-methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects. In: Endocrinology. 2015 ; Vol. 156, No. 5. pp. 1630-1636.
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