Melanogenesis Effect of 7-acetoxy-4-methylcoumarin in B16F10 Melanoma Cells

Ji-Han Sim,Tae-Jin Park,Sung-Chan Jang,Won-Jae Chi,Seung-Young Kim

doi:10.3390/cosmetics7040094

Abstract

The increased interest in anti-whitening dyes has enhanced the research interest to identify efficient melanogenic activators. Melanogenesis is the process of melanin production by melanocytes in the hair follicles and skin, which is mediated by several enzymes, such as microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein (TRP)-1, and TRP-2. This study investigated the melanogenesis-stimulating effect of 4-Methylumbelliferone (4MUMB) and its synthetic derivatives, 7-acetoxy-4-methylcoumarin (7A4MC) and 4-methylheriniarin (4MH) in B16F10 melanoma cells. The cytotoxicity of these compounds was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, followed by the assessment of the melanin content and the intracellular TYR activity. Finally, the expression levels of the key enzymes involved in melanogenesis were investigated. 7A4MC increased melanin production in B16F10 cells relative to that by 4MUMB and 4MH treated cells in a dose-dependent manner without significant cytotoxicity. Concomitantly, 7A4MC significantly increased TYR activity and enhanced the expression of MITF, which significantly induced the expression of TRP-1, TRP-2, and TYR. Furthermore, 7A4MC stimulated melanogenesis via increased phosphorylation of c-Jun N-terminal kinases (JNK) and reduced phosphorylation of protein kinase B (AKT). These results confirmed the melanogenesis-inducing effects of 7A4MC and indicated its potential use as an anti-hair bleaching agent in cosmetics industries.

Highlights

A black/brown skin pigment produced by melanocytes in the skin through the complex process of melanogenesis, determines the color of the eyes and hair and protects the skin against the damage induced by UV radiation (UVR) [1,2]
Acetylation and methylation reactions were investigated using electrospray ionization-mass spectrometry (ESI/MS), and the resulting 7A4MC and 4MH were purified by preparative
We investigated the melanogenic effects of 4MUMB, a hydroxycoumarin and its derivatives, 7A4MC and 4MH

Summary

Introduction

A black/brown skin pigment produced by melanocytes in the skin through the complex process of melanogenesis, determines the color of the eyes and hair and protects the skin against the damage induced by UV radiation (UVR) [1,2]. The increase in the common use of anti-whitening hair dyes in cosmetic industries has increased the interest in identifying novel sources of melanogenesis activators [3]. UV radiation (UVR) is absorbed by different cellular chromophores present in the skin, such as melanin, proteins, amino acids, RNA, DNA, and other biomolecules. Excessive exposure of UVR induces several photochemical reactions involving reactive oxygen species (ROS), leading to skin damage [1]. UV-induced DNA damage activates the binding of the transcription factor, p53, to the promoter of the pro-opiomelanocortin (POMC)

Methods

Results

Conclusion