Potentiation of antiproliferative effects of tamoxifen and ethanol on mouse hepatoma cells by melatonin: possible involvement of mitogen-activated protein kinase and induction of apoptosis

2002 ◽  
Vol 33 (1) ◽  
pp. 8-13 ◽  
Author(s):  
R. Hermann ◽  
S. Podhajsky ◽  
S. Jungnickel ◽  
A. Lerchl
Keyword(s):  
Protein Kinase ◽  
Hepatoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
Antiproliferative Effects ◽  
Mouse Hepatoma ◽  
Mitogen Activated Protein ◽  
Induction Of Apoptosis

Cell-cycle–dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1823-1834 ◽  
Author(s):  
Michael A. Morgan ◽  
Oliver Dolp ◽  
Christoph W. M. Reuter
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Mitogen Activated Protein Kinase ◽  
Ras Signaling ◽  
Myeloid Leukemias ◽  
Mitogen Activated Protein ◽  
Induction Of Apoptosis

Disruption of the RAS–to–mitogen-activated protein kinase (MAPK/ERK) signaling pathway, either directly through activatingRAS gene mutations or indirectly through other genetic aberrations, plays an important role in the molecular pathogenesis of myeloid leukemias. Constitutive activation of ERK-1/2 and MEK-1/2, which elicit oncogenic transformation in fibroblasts, has recently been observed in acute myeloid leukemias (AML). In this study, the activation of the RAS-to-MAPK cascade in 14 AML and 5 chronic myeloid leukemia (CML) cell lines is examined and correlated with the effects of a panel of 9 RAS signaling inhibitors on cell viability, colony formation, cell-cycle progression, and induction of apoptosis. Activation of MEK, ERK, and the transcription factors CREB-1, ATF-1, and c-Myc is demonstrated in the majority of the cell lines (9 of 14 AML and 2 of 5 CML cell lines). Although activation of the ERK cascade did not always correlate with the presence of activatingRAS mutations or BCR-Abl, it is linked to the G0/G1 and the G2/M phase of the cell cycle. In contrast to most inhibitors (eg, B581, Cys-4-Abs-Met, FPT-2, FTI-276, and FTS), a significant growth inhibition was only observed for FTI-277 (19 of 19), FPT-3 (10 of 19), and the MEK inhibitors U0126 (19 of 19) and PD098059 (8 of 19). Treatment of NB-4 cells with FTI-277 primarily resulted in a G2/M block, whereas treatment with FPT-3 and U0126 led to induction of apoptosis. FTI-277 revealed strong toxicity toward normal purified CD34+ cells. The results suggest differences in the mechanisms of action and support a potential therapeutic usefulness of these inhibitors in the treatment of myeloid leukemias.

scholarly journals Mitogen-activated protein kinase pathway is pivotal for anoikis resistance in metastatic hepatoma cells

2014 ◽  
Vol 9 (4) ◽  
pp. 1121-1127 ◽  
Author(s):  
LILI CAO ◽  
ZHIYONG ZHANG ◽  
LIHUI HAN ◽  
JUAN DU ◽  
XIAOHONG LIANG ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
Anoikis Resistance ◽  
Mitogen Activated Protein ◽  
Kinase Pathway
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