Clinical and experimental dermatology · 2014
Inhibitory effects of imatinib mesylate on human epidermal melanocytes.
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Wang Y, Zhao Y, Liu L, Zhang L, Xiao H, Wu K, Xu Y, Hu Y, Fu H, Cao W, Luo Y, Huang H
Аннотация
BACKGROUND: In recent years, increasing attention has been focused on the skin hypopigmentation that develops after the initiation of imatinib mesylate therapy in patients with chronic myeloid leukaemia (CML).
AIM: To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders.
METHODS: We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study.
RESULTS: We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose-dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia-associated transcription factor (MiTF). Furthermore, stem cell factor (SCF)-stimulated c-Kit activation and melanocyte proliferation were completely abrogated by imatinib.
CONCLUSIONS: Inactivation of c-Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined.
AIM: To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders.
METHODS: We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study.
RESULTS: We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose-dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia-associated transcription factor (MiTF). Furthermore, stem cell factor (SCF)-stimulated c-Kit activation and melanocyte proliferation were completely abrogated by imatinib.
CONCLUSIONS: Inactivation of c-Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined.
Предметные рубрики MeSH
BenzamidesCell ProliferationCell SurvivalEpidermal CellsFibroblastsHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMelaninsMelanocytesMicrophthalmia-Associated Transcription FactorModels, BiologicalMonophenol MonooxygenasePiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-kitPyrimidinesSignal TransductionStem Cell FactorTumor Cells, Cultured