Sanguinarine-Induced Apoptosis in Human Leukemia U937 Cells via Bcl-2 Downregulation and Caspase-3 Activation

Chemotherapy ◽  
2008 ◽  
Vol 54 (3) ◽  
pp. 157-165 ◽  
Author(s):  
Min Ho Han ◽  
Young Hyun Yoo ◽  
Yung Hyun Choi
Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3368-3375 ◽  
Author(s):  
Nozomi Niitsu ◽  
Yuri Yamaguchi ◽  
Masanori Umeda ◽  
Yoshio Honma

Abstract The adenosine deaminase (ADA) inhibitor 2′-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2′-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia. © 1998 by The American Society of Hematology.


2009 ◽  
Vol 23 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Cheng-Yun Jin ◽  
Cheol Park ◽  
Jun-Hyuk Lee ◽  
Kyung Tae Chung ◽  
Taeg Kyu Kwon ◽  
...  

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 527 ◽  
Author(s):  
Jing-Ting Chiou ◽  
Yi-Jun Shi ◽  
Liang-Jun Wang ◽  
Chia-Hui Huang ◽  
Yuan-Chin Lee ◽  
...  

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.


2005 ◽  
Vol 28 (12) ◽  
pp. 2338-2341 ◽  
Author(s):  
Mayuko Ujibe ◽  
Syu-ichi Kanno ◽  
Yu Osanai ◽  
Kimiko Koiwai ◽  
Takaharu Ohtake ◽  
...  

2013 ◽  
Vol 23 (9) ◽  
pp. 1118-1125 ◽  
Author(s):  
Cheol Park ◽  
Cheng-Yun Jin ◽  
Tae Hyun Choi ◽  
Su Hyun Hong ◽  
Yung Hyun Choi

2015 ◽  
Vol 231 (1) ◽  
pp. 130-141 ◽  
Author(s):  
Chia-Hui Huang ◽  
Ying-Jung Chen ◽  
Tzu-Yu Chao ◽  
Wen-Hsin Liu ◽  
Jung-Jung Changchien ◽  
...  

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