Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.
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.
Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.|Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.
Nanase
N
Ishii
Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.|Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.
Mizuyuki
M
Ryu
Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.|Lactoferrin Laboratory, Saraya Co. Ltd., 24-12 Tamate-cho, Kashiwara, Osaka, Japan, 582-0028.
Yasushi A
YA
Suzuki
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D000890:Anti-Infective Agents; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D007781:Lactoferrin
MITF; melanin; mélanine, modèle de peau à trois dimensions, tyrosinase, MITF, transduction de signal; signal transduction; three-dimensional skin model; tyrosinase