PHII-7 inhibits cell growth and induces apoptosis in leukemia cell line K562 as well as its MDR- counterpart K562/A02 through producing reactive oxygen species

Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.

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Stress-induced activation of the p53 tumor suppressor in leukemia cells and normal lymphocytes requires mitochondrial activity and reactive oxygen species

Blood ◽

10.1182/blood-2004-09-3428 ◽

2005 ◽

Vol 105 (12) ◽

pp. 4767-4775 ◽

Cited By ~ 47

Author(s):

Leonid Karawajew ◽

Peter Rhein ◽

Grit Czerwony ◽

Wolf-Dieter Ludwig

Keyword(s):

Reactive Oxygen Species ◽

Leukemia Cell ◽

Reactive Oxygen ◽

Leukemia Cell Line ◽

Leukemia Cells ◽

Mitochondrial Activity ◽

Protein Accumulation ◽

Slight Reduction ◽

Oxygen Species ◽

P53 Activation

Abstract The p53 system is highly stress sensitive and integrates diverse intracellular signals in a complex and poorly defined manner. We report on the high dependence of stress-induced p53 activation on mitochondrial activity. Down-regulation of mitochondrial transmembrane potential (MTMP) by inhibitors of electron transport (rotenone, thenoyltrifluoroacetone (TTFA)) and adenosine triphosphate (ATP) synthesis (oligomycin) prevented stress-induced p53 protein accumulation and abrogated p53-dependent apoptosis in a wild-type p53 leukemia cell line MOLT-3, in primary leukemia cells and in normal T lymphocytes. Using genome-wide gene expression analysis, stress-induced up-regulation of the p53 transcriptional targets and their specific inhibition by oligomycin has been demonstrated. Oligomycin did not impair p53-independent apoptosis and caused only a slight reduction of intracellular ATP levels. Reactive oxygen species (ROS) localized to mitochondria decreased in the presence of oligomycin, and stress-induced p53 activation showed strong ROS sensitivity both in leukemic and normal cells. These observations identify mitochondrial activity, described by MTMP and ROS levels, as a critical intracellular determinant of the p53 stress sensitivity and suggest potential implications of this linkage in the mechanisms of chemoresistance of acute leukemia cells. (Blood. 2005;105:4767-4775)

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A novel organobismuth compound, 1-[(2-di-p-tolylbismuthanophenyl)diazenyl]pyrrolidine, induces apoptosis in the human acute promyelocytic leukemia cell line NB4 via reactive oxygen species

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2012.09.009 ◽

2012 ◽

Vol 117 ◽

pp. 77-84 ◽

Cited By ~ 15

Author(s):

Kengo Onishi ◽

Mizuho Douke ◽

Taisuke Nakamura ◽

Youta Ochiai ◽

Naoki Kakusawa ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Line ◽

Acute Promyelocytic Leukemia ◽

Leukemia Cell ◽

Promyelocytic Leukemia ◽

Leukemia Cell Line ◽

Oxygen Species ◽

Acute Promyelocytic Leukemia Cell ◽

Human Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia Cell Line

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Nanotechnologies. 5-(and 6)-Chloromethyl-2',7' Dichlorodihydrofluorescein diacetate (CM-H2DCF- DA) assay for evaluating nanoparticle-induced intracellular reactive oxygen species (ROS) production in RAW 264.7 macrophage cell line

10.3403/30284328u ◽

2016 ◽

Keyword(s):

Reactive Oxygen Species ◽

Cell Line ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Raw 264.7 ◽

Ros Production ◽

Oxygen Species ◽

Macrophage Cell Line ◽

Macrophage Cell ◽

Raw 264.7 Macrophage

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Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

Drug Research ◽

10.1055/a-0762-3775 ◽

2019 ◽

Vol 69 (10) ◽

pp. 528-536

Author(s):

Najat Bouchmaa ◽

Reda Ben Mrid ◽

Youness Boukharsa ◽

Youssef Bouargalne ◽

Mohamed Nhiri ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Anticancer Activity ◽

Cell Line ◽

Cytotoxic Effect ◽

Redox Homeostasis ◽

Reactive Oxygen ◽

Cytotoxic Activities ◽

Oxygen Species ◽

P815 Cell

Abstract Background In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line. Methods The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined. Results The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6f and 7h) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6f and 7h could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6f or 7h with Methotrexate exhibited a synergistic cytotoxic effect. Conclusions considering their significant anticancer activity and chemosensitivity, 6f and 7h may improve the therapeutic efficacy of the current treatment for cancer.

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