Chrysin inhibited stem cell factor (SCF)/c-Kit complex-induced cell proliferation in human myeloid leukemia cells.
Stem cell factor (SCF) has important roles in the proliferation and differentiation of hematopoietic stem cells. The complex of c-Kit and its ligand SCF induce hematopoiesis, melanogenesis, and gametogenesis. However, the mechanism by which SCF induces cell proliferation in the human megakaryoblastic leukemia cell line, MO7e, and the signaling molecules involved, especially in downstream signaling of c-Kit, remain unclear. Here, we show that pharmacological inhibition of the PI3K pathway inhibits SCF/c-Kit signaling and cell proliferation. In addition, we find that the Shc/PDK1/PKC/Akt/c-raf signaling cascade is essential for SCF/c-Kit signal pathway. Our results also suggest that ERK5 is activated and translocated to the nucleus, activating CREB and STAT3. Interestingly, chrysin shuts down the SCF/c-Kit complex-induced signaling cascade. Taken together, these studies give additional insight into the molecular mechanism of SCF/c-Kit-induced cell proliferation and its inverse agonist, chrysin. Finally, these findings enhance our understanding of MO7e cell proliferation.
Lee
Seong Jin
SJ
Pharmaceutical Screening Team, Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Yoon
Joo-Heon
JH
Song
Kyoung Seob
KS
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000502:physiology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005419:Flavonoids; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019089:Stem Cell Factor; C043561:chrysin; D048049:Extracellular Signal-Regulated MAP Kinases; D048054:Mitogen-Activated Protein Kinase 7