Inhibitory effects of imatinib mesylate on human epidermal melanocytes.
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).


OBJECTIVE
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.
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.
Y
Y
Wang
Y
Y
Zhao
L
L
Liu
L
L
Zhang
H
H
Xiao
K
K
Wu
Y
Y
Xu
Y
Y
Hu
H
H
Fu
W
W
Cao
Y
Y
Luo
H
H
Huang
D001549:Benzamides / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000502:physiology; D014407:Tumor Cells, Cultured
D001549:Benzamides; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019089:Stem Cell Factor; D000068877:Imatinib Mesylate; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit