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Effects of dasatinib on skin pigmentation

초록/요약

Background: Dasatinib is a small molecule tyrosine kinase inhibitor that has activity against Src and c-Kit tyrosine kinases. Cases of dasatinib on skin pigmentation were examined have been reported. Objective The effects on dasatinib on skin pigmentation were examined. Methods: The effects on pigmentation were investigated by measuring melanin contents, tyrosinase activity and MITF and tyrosinase expressions in B16 melanoma cells and normal human melanocytes. The pigmentation were also assessed in the ex vivo skin. To explain the mechanism of dasatinib, ERK signaling pathway were examined. Results: Dasatinib treatment increased melanin contents and tyrosinase activity and MITF expression, which eventually led to pigmentation in melanocytes. The stimulatory action of dasatinib in pigmentation was further shown in ex vivo cultured skin. Furthermore, the molecular mechanism underlying the melanogenic effect of dasatinib was associated with the ERK-dependent phosphorylation of CREB. The ERK inhibitor PD98059 not only inhibited the phosphorylation of CREB but also abrogated dasatinib-induced melanocyte differentiation. Conclusion: Dasatinib induced skin pigmentation. These data suggest that dasatinib is a potential therapeutic for hypopigmentary disorders.

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목차

제 1장 INTRODUCTION 1
제 2장 MATERIAL AND METHOD 4
1 Material 4
2 Cell culture 4
3 Cell viability 4
4 Apoptosis assay 5
5 Melanin content and tyrosinase activity 5
6 Real-time PCR analysis 6
7 Western blot analysis 6
8 Ex vivo skin organ culture and pigmentation assay 7
9 Enzyme-linked immunosorbent assay(ELISA) 7
10 Statistical analysis 8
제 3장 RESULTS 9
1 Dasatinib induces pigmentation of B16 melanoma cells. 9
2 Dasatinib induces the melanogenesis of normal human melanocytes at subtoxic concentrations. 13
3 Dasatinib increases cutaneous pigmentation. 19
4 Dasatinib stimulates melanogenesis through the ERK-CREB signaling pathway. 22
제 4장 DISCUSSION 32
제 5장 REFERENCES 36

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