Apoptosis in Human Leukemic Cells Induced by Lactoferricin, a Bovine Milk Protein-Derived Peptide: Involvement of Reactive Oxygen Species

1997 ◽  
Vol 237 (3) ◽  
pp. 624-628 ◽  
Author(s):  
Yung-Choon Yoo ◽  
Ryosuke Watanabe ◽  
Yuko Koike ◽  
Manabu Mitobe ◽  
Kei-ichi Shimazaki ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Milk Protein ◽  
Bovine Milk ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Oxygen Species ◽  
Human Leukemic Cells

scholarly journals Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide andMucuna macrocarpaStem Extract in Human Leukemic Cells via a Reactive Oxygen Species-Dependent Mechanism

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Kuan-Hung Lu ◽  
Hui-Ju Lee ◽  
Min-Li Huang ◽  
Shang-Chih Lai ◽  
Yu-Ling Ho ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Arsenic Trioxide ◽  
Reactive Oxygen ◽  
Butylated Hydroxytoluene ◽  
Leukemic Cells ◽  
Human Leukemia ◽  
Oxygen Species ◽  
Folk Remedy ◽  
Human Leukemic Cells ◽  
Dependent Mechanism

The objective of this study was to examine the potential of enhancing the antileukemic activity of arsenic trioxide (ATO) by combining it with a folk remedy, crude methanolic extract ofMucuna macrocarpa(CMEMM). Human leukemia cells HL-60, Jurkat, and Molt-3 were treated with various doses of ATO, CMEMM, and combinations thereof for 24 and 48 h. Results indicated that the combination of 2.5 μM ATO and 50 μg/mL CMEMM synergistically inhibited cell proliferation in HL-60 and Jurkat cell lines. Apoptosis triggered by ATO/CMEMM treatment was confirmed by accumulation of cells in the sub-G1phase in cell cycle analyses, characteristic apoptotic nuclear fragmentation, and increased percentage of annexin V-positive apoptotic cells. Such combination treatments also led to elevation of reactive oxygen species (ROS). The antioxidantsN-acetyl cysteine (NAC), butylated hydroxytoluene, andα-tocopherol prevented cells from ATO/CMEMM-induced apoptosis. The ATO/CMEMM-induced activation of caspase-3 and caspase-9 can be blocked by NAC. In summary, these results suggest that ATO/CMEMM combination treatment exerts synergistic apoptosis-inducing effects in human leukemic cells through a ROS-dependent mechanism and may provide a promising antileukemic approach in the future.

scholarly journals Denbinobin inhibits nuclear factor-κB and induces apoptosis via reactive oxygen species generation in human leukemic cells

2009 ◽  
Vol 77 (8) ◽  
pp. 1401-1409 ◽  
Author(s):  
Gonzalo Sánchez-Duffhues ◽  
Marco A. Calzado ◽  
Amaya García de Vinuesa ◽  
Giovanni Appendino ◽  
Bernd L. Fiebich ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Nuclear Factor Κb ◽  
Leukemic Cells ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Human Leukemic Cells

The Requirement of Reactive Oxygen Species Generation in the Apoptosis of Leukemia Cells Induced by 2-Methoxyestradiol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4370-4370
Author(s):  
Guo Kunyuan ◽  
Miaorong She ◽  
Haiyan Hu ◽  
Xinqing Niu ◽  
Sanfang Tu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Leukemia Cell ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract 2-Methoxyestradiol (2-ME) is a new anticancer agent currently under investigation for treatment of leukemia. We evaluated the effects of 2-ME-induced apoptosis in two myeloid leukemia cell lines (U937 and HL-60) in association with reactive oxygen species (ROS) generation. We found that 2-ME resulted in viability decrease in a dose-dependent manner, generated ROS: nitric oxide and superoxide anions, and mitochondria damage. 2-ME-induced apoptosis correlated with increase in ROS. Quenching of ROS with N-acetyl-L-cysteine protected leukemia cells from the cytotoxicity of 2-ME and prevented apoptosis induction by 2-ME. Furthermore, addition of manumycin, a farnesyltransferase inhibitor, demonstrated by our previous studies that induced apoptosis of leukemic cells and induced ROS, significantly enhanced the apoptosis-induced by 2-ME. In conclusion, cellular ROS generation play an important role in the cytotoxic effect of 2-ME. It is possible to use ROS-generation agents such as manumycin to enhance the antileukemic effect. Such a combination strategy need the further in vivo justify and may have potential clinical application.

Embelin-Mediated Apoptosis in Leukemic Cells via Generation of Reactive Oxygen Species

2016 ◽  
Author(s):  
Shahab Uddin Khan ◽  
Kirti S Prabhu ◽  
Siveen Sivaraman ◽  
Ahmad Iskandrani ◽  
Shilpa Kuttikrishnan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Oxygen Species

Reactive Oxygen Species Target the Degradation of the EVI1 Oncoprotein.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 651-651
Author(s):  
David Shackelford ◽  
You Wang ◽  
Samuel Waxman ◽  
Ruibao Ren
Keyword(s):  
Reactive Oxygen Species ◽  
De Novo ◽  
Bone Marrow Cells ◽  
Reactive Oxygen ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Mouse Bone Marrow ◽  
Oxygen Species ◽  
Aberrant Expression

Abstract Aberrant expression of EVI1 has been frequently found in myeloid malignancies as well as in cancers of the ovary, lung, head and neck, cervix, and breast, and is associated with a poor patient survival. Targeted degradation of oncoproteins is an effective strategy for cancer therapy. The AML1/MDS1/EVI1 (AME) transcription factor fusion protein is a product of the human t(3;21)(q26;q22) translocation found as a secondary mutation in some cases of CML during the blast phase (CML-BP) and in patients with de novo and therapy-related myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Expression of AME in mouse bone marrow cells by retroviral transduction impairs hematopoiesis and eventually induces an acute myeloid leukemia (AML)-like disease in mice. Arsenic Trioxide (ATO) has been found to be an effective treatment for patients suffering from acute promyelocytic leukemia (APL). This is, at least in part, mediated by degradation of the PML/RARα oncoprotein that is associated with over 90% of APL. We have recently shown that ATO used at therapeutic levels also degrades AME. The ATO treatment induces differentiation and apoptosis in AME leukemic cells in vitro and causes decrease in peripheral leukemic cells and splenomegaly in vivo. ATO appears to target AME at both the EVI1 and MDS moieties of the protein for degradation via the ubiquitin-proteasome pathway and proteasome-independent mechanism, respectively. To investigate the mechanism of ATO induced degradation of EVI1 oncoproteins, we examined the effect of reactive oxygen species (ROS), on EVII expression, one of the downstream effectors of ATO-induced apoptosis. We found that EVI1 degradation correlates with the amount of ROS generated in cells. EVI1 can also be targeted for degradation by doxorubicin, a chemotherapeutic agent that is effective in treating AML and ovarian cancer and a strong ROS inducer. Interestingly, the antioxidant N-acetyl cysteine (NAC) abrogates the degradation of the EVI1 protein in the presence of doxorubicin. These results demonstrate that EVI1 can be targeted for degradation by ROS. ROS inducing agents could be used as a part of targeted therapy for EVI1-positive malignancies.

Tetraarsenic oxide induces apoptosis in U937 leukemic cells through a reactive oxygen species-dependent pathway

2003 ◽  
Author(s):  
In-Chul Park ◽  
Myung-Jin Park ◽  
Sang-Hyeok Woo ◽  
Hyung-Chahn Lee ◽  
Sungkwan An ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Oxygen Species ◽  
Dependent Pathway

Green Tea Component, Catechin, Induces Apoptosis of Myeloid Leukemic Cells Via Myeloperoxidase (MPO)-Dependent Highly Reactive Oxygen Species (ROS) Production.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4429-4429
Author(s):  
Tomonori Nakazato ◽  
Kenji Yamato ◽  
Morihiko Sagawa ◽  
Yuriko Nishiyama ◽  
Yasuo Ikeda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Green Tea ◽  
Reactive Oxygen ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type ◽  
Halide System ◽  
Induced Apoptosis

Abstract Green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), has a potent chemopreventive effects against various tumors, and epidemiologic studies have suggested that green tea consumption might be effective for reducing the incidence of certain cancers. We have reported that EGCG rapidly induces apoptosis of myeloid leukemic cells via modulation of reactive oxygen species (ROS) production in vitro and in vivo (Haematologica2005;90:317). In this study, we further examined the precise mechanism of EGCG-induced apoptosis and its relationship to the heme enzyme myeloperoxidase (MPO). EGCG inhibited cellular growth of various myeloid leukemic cells via induction of apoptosis in dose- and time-dependent manners. Interestingly, EGCG rapidly induced apoptosis in MPO-positive myeloid leukemic cell lines (HL-60, UF-1, NB4, Kasumi-1) and fresh myeloid leukemic cells from patients, whereas EGCG failed to induce apoptosis in MPO-negative leukemic cells (U937, THP-1, KG-1, K562). Pre-incubation of MPO-positive myeloid leukemic cells with the MPO-specific inhibitor, 4-aminobenzoic acid hydrazide (50 μM), and the heme biosynthesis inhibitor, succinylacetone (0.5 mM), resulted in significant inhibition of intracellular MPO activity, ROS production, and induction of apoptosis after treatment with 50 μM EGCG. Pre-incubation of MPO-positive myeloid leukemic cells with anti-oxidant, catalase, completely suppressed EGCG-induced ROS production and apoptosis. These results indicate that EGCG-induced apoptosis is mediated through the generation of hydrogen peroxide (H2O2). To investigate the role of MPO in EGCG-induced apoptosis of leukemic cells, MPO-negative K562 cells were stably transfected with full length of MPO cDNA (K562/MPO cells). Marked interest, K562/MPO cells induced MPO activity, intracellular ROS production, and enhanced susceptibility of cells to EGCG-induced apoptosis compared to wild-type K562 cells. These results suggested that MPO positivity may be important to determine the sensitivity to EGCG-induced apoptosis, and MPO-derived ROS are involved in apoptosis in myeloid leukemic cells. MPO catalyzes the formation of hypochlorous acid (HOCl), a powerful oxidant formed from Cl− and H2O2. Therefore, we next examined the relationship between EGCG-induced apoptosis and H2O2/MPO/halide system in MPO-positive HL-60 cells. Addition of HOCl scavengers, methionine (10 mM) and taurine (25 mM), inhibited EGCG-induced apoptosis in HL-60 and K562/MPO cells, but not wild-type K562 cells, suggesting that HOCl is the mediator of EGCG-induced apoptosis. Interestingly, hydroxyl radical (•OH) scavenger, thiourea, also inhibited EGCG-induced apoptosis in HL-60 cells. To determine which reactive oxygen species play a key role in EGCG-induced apoptosis mediated through MPO, we used novel fluorescence probes APF and HPF, which can detect selectively highly ROS (hROS). It is noteworthy that the fluorescence intensity of both APF- and HPF-loaded HL-60 cells significantly increased upon stimulation with EGCG, suggesting that EGCG generated hROS (•OH, ONOO−) and OCl−, but not other ROS (H2O2, NO, O2−, 1O2) in HL-60 cells. Taken together, these results indicated that highly toxic ROS such as hydroxyl radical generated via H2O2/MPO/halide system induces apoptosis, and that it may be the direct mediator of EGCG-induced apoptosis in MPO-positive myeloid leukemic cells.

scholarly journals Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells

2008 ◽  
Vol 32 (5) ◽  
pp. 771-780 ◽  
Author(s):  
Shan Gao ◽  
Aaron Mobley ◽  
Claudia Miller ◽  
Jessica Boklan ◽  
Joya Chandra
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Oxygen Species ◽  
Synergistic Cytotoxicity
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