Ganglioside GM3 is required for caffeic acid phenethyl ester-induced megakaryocytic differentiation of human chronic myelogenous leukemia K562 cells

2014 ◽  
Vol 92 (4) ◽  
pp. 243-249 ◽  
Author(s):  
Un-Ho Jin ◽  
Tae-Wook Chung ◽  
Kwon-Ho Song ◽  
Choong-Hwan Kwak ◽  
Hee-Jung Choi ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
K562 Cells ◽  
Caffeic Acid Phenethyl Ester ◽  
Camp Response Element Binding ◽  
Myelogenous Leukemia ◽  
Ganglioside Gm3 ◽  
Megakaryocytic Differentiation ◽  
Gm3 Synthase ◽  
Element Binding Protein ◽  
Characteristic Features

The human chronic myelogenous cell line K562 has been used extensively as a model for the study of leukemia differentiation. We show here that treatment of K562 cells with caffeic acid phenethyl ester (CAPE) induced a majority of cells to differentiate towards the megakaryocytic lineage. Microscopy analysis showed that K562 cells treated with CAPE exhibited characteristic features of physiological megakaryocytic differentiation, including the presence of vacuoles and demarcation membranes. Differentiation of K562 cells treated with CAPE was also accompanied by a net increase in megakaryocytic markers. The transcriptional activity of lactosylceramide α-2,3-sialyltransferase (GM3 synthase) and synthesis of ganglioside GM3 were increased by CAPE treatment. The promoter analysis of GM3 synthase demonstrated that CAPE induced the expression of GM3 synthase mRNA via activation of the cAMP response element-binding protein (CREB), transcription factor in nucleus. Interestingly, the inhibition of ganglioside GM3 synthesis by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol (D-PDMP) and GM3 synthase-siRNA blocked the CAPE-induced expression of the megakaryocytic markers and differentiation of K562 cells. Taken together, these results suggest that CAPE induces ganglioside GM3-mediated megakaryocytic differentiation of human chronic myelogenous cells.

cAMP response element-binding protein 1 is required for hydroxyurea-mediated induction of γ-globin expression in K562 cells

2012 ◽  
Vol 39 (6) ◽  
pp. 510-517 ◽  
Author(s):  
Mehdi Banan ◽  
Elika Esmaeilzadeh-Gharehdaghi ◽  
Majid Nezami ◽  
Zahra Deilami ◽  
Samaneh Farashi ◽  
...  
Keyword(s):  
Binding Protein ◽  
K562 Cells ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein

scholarly journals Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e29014 ◽  
Author(s):  
Huey-Lan Huang ◽  
Yu-Chieh Chen ◽  
Yu-Chuen Huang ◽  
Kai-Chien Yang ◽  
Hsin yi Pan ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Megakaryocytic Differentiation

Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl+ K562 leukemic cells by Gab2

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1388-1397 ◽  
Author(s):  
Jay F. Dorsey ◽  
Jess M. Cunnick ◽  
Shrikant M. Mane ◽  
Jie Wu
Keyword(s):  
Map Kinase ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Transcriptional Activation ◽  
Blast Crisis ◽  
Terminal Differentiation ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Megakaryocytic Differentiation

In the blast crisis phase of chronic myelogenous leukemia (CML), Bcr-Abl+ myeloblasts fail to undergo terminal maturation. The extracellular signal–regulated kinase (Erk) mitogen-activated protein (MAP) kinase has been shown to mediate terminal differentiation of myeloid cells. Interestingly, Bcr-Abl+ CML cell lines established from blast crisis were found to have low Erk MAP kinase activity. In this study, we analyzed the role of the Gab2 docking protein in regulation of the Erk MAP kinase in Bcr-Abl+K562 human CML cells. Overexpression of Gab2 in K562 cells resulted in transcriptional activation of the c-fos serum response element (SRE) promoter, whereas overexpression of SHP2, Grb2, and CrkL had no effect. Activation of the c-fos SRE transcriptional activity by Gab2 required tyrosine 604, which is a SHP2 docking site on Gab2, and the SHP2 tyrosine phosphatase activity. Elk1, c-Jun, and CHOPtrans-reporting assays indicated that overexpression of Gab2 selectively activated the Erk2-Elk1 signaling pathway. To determine cellular consequences of elevating the Gab2 level in K562 cells, stable cell lines for doxycycline-inducible expression of the wild-type Gab2 (Gab2WT) and an SHP2-binding defective Gab2 (Gab2Tyr604Phe) were established. Analysis of these cell lines indicated that induction of Gab2WT expression, but not Gab2Tyr604Phe expression, led to Erk activation, growth arrest, cell spreading, and enlargement; expression of megakaryocyte/platelet lineage–specific integrins αIIb/β3 (CD41/CD61); and upregulation of RNA for megakaryocyte/platelet proteins. All of these changes are characteristics of megakaryocytic differentiation. Together, these results reveal Gab2 as a limiting signaling component for Erk MAP kinase activation and terminal differentiation of K562 CML cells.

Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang
Keyword(s):  
Protein Kinase ◽  
Bone Pain ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Dependent Protein Kinase ◽  
Response Element ◽  
Protein Kinase Ii ◽  
Element Binding Protein ◽  
Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

Novel Caffeic Acid Phenethyl Ester (Cape) Analogues as Inducers of Heme Oxygenase-1

2017 ◽  
Vol 23 (18) ◽  
Author(s):  
Valeria Pittala ◽  
Luca Vanella ◽  
Loredana Salerno ◽  
Claudia Di Giacomo ◽  
Rosaria Acquaviva ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Heme Oxygenase ◽  
Caffeic Acid Phenethyl Ester ◽  
Heme Oxygenase 1
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