Pharmacological inhibition of the MAPK/ERK pathway increases sensitivity to 2-chloro-2′-deoxyadenosine (CdA) in the B-cell leukemia cell line EHEB

2007 ◽  
Vol 73 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Caroline Smal ◽  
Stéphanie Lisart ◽  
Marie Maerevoet ◽  
Augustin Ferrant ◽  
Françoise Bontemps ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Erk Pathway ◽  
Cell Leukemia ◽  
Pharmacological Inhibition ◽  
B Cell Leukemia

Inhibition of the ERK Pathway Promotes Apoptosis Induced by 2-Chloro-2′-Deoxyadenosine in the B-Cell Leukemia Cell Line Eheb

2006 ◽  
Vol 25 (9-11) ◽  
pp. 1009-1012 ◽  
Author(s):  
C. Smal ◽  
S. Lisart ◽  
A. Ferrant ◽  
F. Bontemps ◽  
E. Van Den Neste
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Erk Pathway ◽  
Cell Leukemia ◽  
B Cell Leukemia

Chemical Biology Strategy Reveals Cell Lineage- and Cell Differentiation-Specific Small Molecule Inhibitors of NF-κB.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2421-2421
Author(s):  
Hideki Goto ◽  
Paul Diaz ◽  
Shu-ichi Matsuzawa ◽  
Eduard Sergienko ◽  
Steve Vasile ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Leukemia Cell ◽  
Cell Lineage ◽  
Leukemia Cell Line ◽  
Luciferase Reporter ◽  
Cell Leukemia ◽  
B Cell Leukemia ◽  
Specific Inhibitors

Abstract Abstract 2421 Members of the nuclear factor-kB (NF-κB) family of transcription factors play important roles in cell-signaling involved in host-defense, immune responses, inflammation, and cancer. Multiple stimuli operating through different receptors are capable of activating NF-κB, including the Tumor Necrosis Factor (TNF) family cytokines, Toll-like receptors (TLRs), Nucleotide-binding Leucine Rich Repeat Proteins (NLRs), DNA-damaging agents, and others. Drugs that selectively block activation of NF-κB through one or more of these receptors could have activity against various types of cancer in which activation of NF-κB plays a role. We used a chemical biology strategy to identify novel chemical inhibitors of cell pathways responsible for NF-κB activation. Screening of a large chemical library (>330K compounds from NIH) was conducted using human 697 pre-B-cell leukemia cells with a stably integrated NF-κB-luciferase reporter gene and stimulating the Carma/Bcl-10/MALT pathway using protein kinase C (PKC) activators (PMA/Ionomycin). Confirmed hits were counter-screened against HEK293T-NF-κB-luciferase cells treated with TNF-a, with the goal to eliminate non-pathway specific inhibitors of NF-κB. Among the hit compounds, we identified oxadiazole- and oxazole-based chemical probes as potential cell lineage- and cell differentiation-specific inhibitors of NF-κB (“NLDSi” = NF-κB lineage, differentiation-specific inhibitors). Using a panel of cell lines with stably integrated NF-κB-driven luciferase reporter genes, NLDSi compounds suppressed PMA/Ionomycin-induced NF-κB activity in a concentration-dependent manner (IC50=0.1–1.0 μM) in the pre-B-cell leukemia cell-line 697, but not in the T-cell leukemia line JURKAT, the myeloma cell-line RPMI8226, or HEK293 epithelial cells. These compounds also suppressed NF-κB activity (measured by reporter gene) in 697 cells stimulated with BAFF or treated with doxorubicin. Examining NF-κB target gene expression by q-RT-PCR (mRNA level) and immunoblotting (protein level) showed that NLDSi compounds reduced PMA/Ionomycin-induced TRAF1 and A20 expression in 697 cells and in the pre-B-cell leukemia cell line REH, but not in several mature B-cell lines, including BJAB, Daudi, OCILy3, and OCILy10. NLDSi compounds also inhibited NF-κB target gene expression in pre-B-cell lines stimulated with BAFF or treated with lipopolysaccharide (LPS) or doxorubicin (Dox). Nevertheless we found these compounds could suppress of PMA/Ionomycin-induced expression of TRAF1 and A20 gene in the primary leukemia cells of patients with chronic lymphocytic leukemia (CLL). Taken together, the compounds described here appear to selectively suppress NF-κB activation in the B-cell lineage at specific stages of differentiation. As such, these small molecules could serve as chemical probes for uncovering novel targets that regulate NF-κB activity and potentially lead to development of therapies that selectively block certain types of NF-κB activation in pre-B cell ALL, CLL, or other hematologic malignancies. (Supported by NIH grants X01 MH077633-1, U54–005033, and P01-CA-81534). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Establishment and Characterization of a New Canine B-Cell Leukemia Cell Line.

1996 ◽  
Vol 58 (5) ◽  
pp. 469-471 ◽  
Author(s):  
Munekazu NAKAICHI ◽  
Yasuho TAURA ◽  
Masashi KANKI ◽  
Koichi MAMBA ◽  
Yasuyuki MOMOI ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Cell Leukemia ◽  
B Cell Leukemia

Effects of hydroxylated resveratrol analogs on oxidative stress and cancer cells death in human acute T cell leukemia cell line

2014 ◽  
Vol 209 ◽  
pp. 96-110 ◽  
Author(s):  
Malgorzata Kucinska ◽  
Hanna Piotrowska ◽  
Michał W. Luczak ◽  
Justyna Mikula-Pietrasik ◽  
Krzysztof Ksiazek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Cancer Cells ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Resveratrol Analogs ◽  
Cells Death
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