Effect of 7-Methylsulfinylheptyl Isothiocyanate on the Inhibition of Melanogenesis in B16-F1 Cells.

A-Ju Kim,Do Sung Lim,Jung Sup Lee,Yeong Hee Cho,Jung Eun Park

doi:10.3390/life11020162

Abstract

Skin aging, characterized by hyperpigmentation, inflammation, wrinkles, and skin cancer, is influenced by intrinsic and extrinsic factors with synergistic effects. Autophagy maintains the homeostatic balance between the degradation, synthesis, and recycling of cellular proteins and organelles, and plays important roles in several cellular and biological processes, including aging. The compound 7-methylsulfinylheptyl isothiocyanate (7-MSI) is a sulfur-containing phytochemical produced by various plants, particularly cruciferous vegetables, with reported anti-inflammatory properties and a role in pathogen defense; however, its effects on skin whitening have not been studied in detail. The purpose of this study was to observe the effects of 7-MSI on skin whitening and autophagy in cultured murine melanoma (B16-F1) cells. Western blotting was used to evaluate the impact of 7-MSI on melanogenesis-, tyrosinase-, and autophagy-associated proteins. The levels of the melanogenesis-associated protein’s microphthalmia-associated transcription factor (MITF) and tyrosinase and tyrosinase-related protein-1 were decreased by treatment with 7-MSI under melanogenesis induction. Melanin synthesis also decreased by approximately 63% after treatment with 7-MSI for 73 h, compared with that non-treated controls. In addition, autophagosome formation and the expression levels of the autophagy-related proteins mTOR, p-mTOR, Beclin-1, Atg12, and LC3 were higher in 7-MSI-treated B16-F1 cells than in non-treated cells. These results indicate that 7-MSI can inhibit melanin synthesis in B16-F1 cells by suppressing melanogenesis and autophagy activation and thus can potentially be used as a novel multifunctional cosmetic agent.

Highlights

protein kinase A (PKA) phosphorylates cAMP response element-binding protein (CREB), which regulates the expression of the microphthalmia-associated transcription factor (MITF) [3,6,7,8] that controls the production of tyrosinase and tyrosinase-related protein-1/2 (TRP-1/2) [4,9]
The phosphorylation of CREB leads to the expression of MITF, which regulates the production of tyrosinase and TRP-1 [4,36]
In the presence of α-MSH (10 nM)-induced melanin synthesis for 24 h, compared with those in cells treated with α-MSH alone. These results suggest that 7-methylsulfinylheptyl isothiocyanate (7-MSI) can inhibit the expression of melanogenesis-associated proteins

Summary

Introduction

These factors act synergistically, leading to skin aging with cumulative alterations to the skin structure, function, and appearance, which can lead to hyperpigmentation, wrinkle formation, and skin cancer [2,3]. Melanin is synthesized by skin cells to provide protection from UV light exposure [4]. Excessive melanin synthesis in the skin causes hyperpigmentation, which can result in melasma, freckles, and aging-associated pigment spots [5]. UV exposure stimulates the production of alpha-melanocyte-stimulating hormone (α-MSH), which binds to the melanocortin 1 receptor (MC1R) within the cell membrane and activates protein kinase A (PKA). Tyrosinase and TRP1/2 are the main enzymes controlling the production of the two forms of melanin, eumelanin and pheomelanin [13,14]

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