Screening of Kit inhibitors: suppression of Kit signaling and melanogenesis by emodin.
In search of novel antipigmentation agents, a set of 3,840 compounds with natural-like synthetic or natural origin were screened against Kit (stem cell factor receptor). Emodin from the seed of Cassia tora and baicalin from Scutellariae radix showed potent inhibitory effects (IC(50) = 4.9 and 9.0 microM, respectively) on the phosphorylation of Kit. Emodin also blocked other receptor tyrosine kinase activities, such as epithelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR-2), fibroblast growth factor receptor 1 (FGFR-1), platelet-derived growth factor receptor b (PDGFR-b). In contrast to emodin, aloe-emodin did not inhibit Kit activity at all. Emodin also blocked the cellular kinase activities of Kit and its down-stream p44/42 mitogen activated protein kinase (MAPK) in MO7e cells and human primary melanocytes. Emodin strongly suppressed the melanin synthesis triggered by stem cell factor (SCF) treatment. Also, emodin showed almost no toxicity up to 10 microM on cultured melanocytes as reported previously by other researchers. The results indicate that emodin is a good candidate for the development of antipigmentation agents since it can radically block the differentiation and proliferation of pigment cells by reducing Kit signaling.
Lee
Seong Jin
SJ
Pharmacology Research Center, Bio-organic Science Division, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea.
Jeong
Daeyoung
D
Park
Woo-Kyu
WK
Kong
Jae Yang
JY
Choi
Gildon
G
Kim
Hojeong
H
Kang
Sangjin
S
Cho
Heeyeong
H
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes; D015394:Molecular Structure; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
D008543:Melanins; D019009:Proto-Oncogene Proteins c-kit; D004642:Emodin