Ishii Nanase, Ryu Mizuyuki, Suzuki Yasushi A
Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.
Biochem Cell Biol. 2017 Feb;95(1):119-125. doi: 10.1139/bcb-2016-0053. Epub 2017 Jan 19.
The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent.
本研究的目的是评估牛乳铁蛋白（bLf）对黑色素生成细胞的作用，并阐明其作用机制。我们在三维培养的色素沉着皮肤模型上测试了bLf的抗黑色素生成作用，证实色素沉着减少了20%，这表明bLf可经皮吸收并抑制黑色素生成。用bLf处理人黑色素瘤细胞导致黑色素生成受到显著的、剂量依赖性的抑制。脱铁bLf和全铁bLf对黑色素生成的抑制程度与bLf相同。bLf这种抗黑色素生成作用背后的关键特征是小眼相关转录因子（MITF）的下调，从而导致酪氨酸酶活性的抑制。用bLf处理导致MITF mRNA表达降低以及MITF蛋白降解增强。然而，主要效应因子是细胞外信号调节激酶（ERK）磷酸化增强，导致MITF磷酸化和降解。我们发现bLf抑制黑色素细胞中的黑色素生成，这表明bLf可能是一种有应用潜力的皮肤美白剂。
