The Association Between p38 MAPK-Mediated TNF-α/TNFR2 up-Regulation and 2-(4-Aminophenyl)-7-Methoxybenzothiazole-Induced Apoptosis in Human Leukemia U937 Cells

2015 ◽  
Vol 231 (1) ◽  
pp. 130-141 ◽  
Author(s):  
Chia-Hui Huang ◽  
Ying-Jung Chen ◽  
Tzu-Yu Chao ◽  
Wen-Hsin Liu ◽  
Jung-Jung Changchien ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Human Leukemia ◽  
U937 Cells ◽  
Tnf Α ◽  
Induced Apoptosis

CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl–positive human leukemia cells to apoptosis due to antileukemic drugs

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2246-2253 ◽  
Author(s):  
Guofu Fang ◽  
Caryn Naekyung Kim ◽  
Charles L. Perkins ◽  
Nimmanapalli Ramadevi ◽  
Elliott Winton ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Fas Ligand ◽  
Ectopic Expression ◽  
K562 Cells ◽  
Parp Cleavage ◽  
Human Leukemia ◽  
Sti 571 ◽  
Tnf Α ◽  
Cyt C ◽  
Induced Apoptosis

Abstract The differentiation and apoptosis-sensitizing effects of the Bcr-Abl–specific tyrosine kinase inhibitor CGP57148B, also known as STI-571, were determined in human Bcr-Abl–positive HL-60/Bcr-Abl and K562 cells. First, the results demonstrate that the ectopic expression of the p185 Bcr-Abl fusion protein induced hemoglobin in the acute myeloid leukemia (AML) HL-60 cells. Exposure to low-dose cytosine arabinoside (Ara-C; 10 nmol/L) increased hemoglobin levels in HL-60/Bcr-Abl and in the chronic myeloid leukemia (CML) blast crisis K562 cells, which express the p210 Bcr-Abl protein. As compared with HL-60/neo, HL-60/Bcr-Abl and K562 cells were resistant to apoptosis induced by Ara-C, doxorubicin, or tumor necrosis factor-α (TNF-α), which was associated with reduced processing of caspase-8 and Bid protein and decreased cytosolic accumulation of cytochrome c (cyt c). Exposure to CGP57148B alone increased hemoglobin levels and CD11b expression and induced apoptosis of HL-60/Bcr-Abl and K562 cells. CGP57148B treatment down-regulated antiapoptotic XIAP, cIAP1, and Bcl-xL, without affecting Bcl-2, Bax, Apaf-1, Fas (CD95), Fas ligand, Abl, and Bcr-Abl levels. CGP57148B also inhibited constitutively active Akt kinase and NFκB in Bcr-Abl–positive cells. Attenuation of NFκB activity by ectopic expression of transdominant repressor of IκB sensitized HL-60/Bcr-Abl and K562 cells to TNF-α but not to apoptosis induced by Ara-C or doxorubicin. Importantly, cotreatment with CGP57148B significantly increased Ara-C– or doxorubicin-induced apoptosis of HL-60/Bcr-Abl and K562 cells. This was associated with greater cytosolic accumulation of cyt c and PARP cleavage activity of caspase-3. These in vitro data indicate that combinations of CGP57148B and antileukemic drugs such as Ara-C may have improved in vivo efficacy against Bcr-Abl–positive acute leukemia.

Naringenin-induced apoptosis is attenuated by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human leukemia U937 cells

2009 ◽  
Vol 23 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Cheng-Yun Jin ◽  
Cheol Park ◽  
Jun-Hyuk Lee ◽  
Kyung Tae Chung ◽  
Taeg Kyu Kwon ◽  
...  
Keyword(s):  
Small Molecule ◽  
Human Leukemia ◽  
U937 Cells ◽  
Induced Apoptosis

scholarly journals Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca2+/PP2A/AMPK Axis

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 527 ◽  
Author(s):  
Jing-Ting Chiou ◽  
Yi-Jun Shi ◽  
Liang-Jun Wang ◽  
Chia-Hui Huang ◽  
Yuan-Chin Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Damage ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
U937 Cells ◽  
Cell Membrane Damage ◽  
Human Leukemia Cells ◽  
Phosphatase 2A ◽  
Induced Apoptosis ◽  
Naja Atra

Cardiotoxins (CTXs) are suggested to exert their cytotoxicity through cell membrane damage. Other studies show that penetration of CTXs into cells elicits mitochondrial fragmentation or lysosome disruption, leading to cell death. Considering the role of AMPK-activated protein kinase (AMPK) in mitochondrial biogenesis and lysosomal biogenesis, we aimed to investigate whether the AMPK-mediated pathway modulated Naja atra (Taiwan cobra) CTX3 cytotoxicity in U937 human leukemia cells. Our results showed that CTX3 induced autophagy and apoptosis in U937 cells, whereas autophagic inhibitors suppressed CTX3-induced apoptosis. CTX3 treatment elicited Ca2+-dependent degradation of the protein phosphatase 2A (PP2A) catalytic subunit (PP2Acα) and phosphorylation of AMPKα. Overexpression of PP2Acα mitigated the CTX3-induced AMPKα phosphorylation. CTX3-induced autophagy was via AMPK-mediated suppression of the Akt/mTOR pathway. Removal of Ca2+ or suppression of AMPKα phosphorylation inhibited the CTX3-induced cell death. CTX3 was unable to induce autophagy and apoptosis in U937 cells expressing constitutively active Akt. Met-modified CTX3 retained its membrane-perturbing activity, however, it did not induce AMPK activation and death of U937 cells. These results conclusively indicate that CTX3 induces autophagy and apoptosis in U937 cells via the Ca2+/PP2A/AMPK axis, and suggest that the membrane-perturbing activity of CTX3 is not crucial for the cell death signaling pathway induction.

scholarly journals Octylcaffeate Induced Apoptosis in Human Leukemia U937 Cells

2005 ◽  
Vol 28 (12) ◽  
pp. 2338-2341 ◽  
Author(s):  
Mayuko Ujibe ◽  
Syu-ichi Kanno ◽  
Yu Osanai ◽  
Kimiko Koiwai ◽  
Takaharu Ohtake ◽  
...  
Keyword(s):  
Human Leukemia ◽  
U937 Cells ◽  
Induced Apoptosis

Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells

2010 ◽  
Vol 288 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Dong-Oh Moon ◽  
Mun-Ock Kim ◽  
Jae-Dong Lee ◽  
Yung Hyun Choi ◽  
Gi-Young Kim
Keyword(s):  
Cell Death ◽  
Rosmarinic Acid ◽  
Ros Generation ◽  
Human Leukemia ◽  
U937 Cells ◽  
Tnf Α

scholarly journals Naja atra Cardiotoxin 1 Induces the FasL/Fas Death Pathway in Human Leukemia Cells

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2073
Author(s):  
Jing-Ting Chiou ◽  
Liang-Jun Wang ◽  
Yuan-Chin Lee ◽  
Long-Sen Chang
Keyword(s):  
P38 Mapk ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
U937 Cells ◽  
Fasl Expression ◽  
Mechanistic Pathway ◽  
Leukemia Cell Lines ◽  
Sirna Knockdown ◽  
Naja Atra

This study aimed to investigate the mechanistic pathway of Naja atra (Taiwan cobra) cardiotoxin 1 (CTX1)–induced death of leukemia cell lines U937 and HL-60. CTX1 increased cytoplasmic Ca2+ and reactive oxygen species (ROS) production, leading to the death of U937 cells. It was found that Ca2+-induced NOX4 upregulation promoted ROS-mediated p38 MAPK phosphorylation, which consequently induced c-Jun and ATF-2 phosphorylation. Using siRNA knockdown, activated c-Jun and ATF-2 were demonstrated to regulate the expression of Fas and FasL, respectively. Suppression of Ca2+-mediated NOX4 expression or ROS-mediated p38 MAPK activation increased the survival of U937 cells exposed to CTX1. FADD depletion abolished CTX1-induced cell death, caspase-8 activation, and t-Bid production, supporting the correlation between the Fas death pathway and CTX1-mediated cytotoxicity. Among the tested N. atra CTX isotoxins, only CTX1 induced Fas and FasL expression. Chemical modification studies revealed that intact Met residues were essential for the activity of CTX1 to upregulate Fas and FasL expression. Taken together, the data in this study indicate that CTX1 induces c-Jun-mediated Fas and ATF-2-mediated FasL transcription by the Ca2+/NOX4/ROS/p38 MAPK axis, thereby activating the Fas death pathway in U937 cells. Furthermore, CTX1 activates Fas/FasL death signaling in the leukemia cell line HL-60.

scholarly journals Effect of Proapoptotic Bcl-2 on Naringenin-induced Apoptosis in Human Leukemia U937 Cells

2013 ◽  
Vol 23 (9) ◽  
pp. 1118-1125 ◽  
Author(s):  
Cheol Park ◽  
Cheng-Yun Jin ◽  
Tae Hyun Choi ◽  
Su Hyun Hong ◽  
Yung Hyun Choi
Keyword(s):  
Human Leukemia ◽  
U937 Cells ◽  
Induced Apoptosis
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