Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous data showed that JWA might be a novel environmental responsive gene regulated by environmental stressors such as heat shock and oxidative stress. However, the molecular mechanism underlying JWA gene function involved in oxidative stress is still unknown. In this study, the potential role of JWA was further investigated in hydrogen peroxide (H2O2) induced DNA damage and cell apoptosis in K562 cells. Series of the oxidative stress models were established to observe if JWA was involved in DNA damage or cell apoptosis induced by H2O2 exposure. These results indicated that the inhibitory effect on K562 cells' viability induced by H2O2 was concentration and time dependent. JWA was more sensitive to H2O2 (0.01 mmol/L) than the heat-shock proteins (hsp70 and hsp27), and its expression pattern was similar to that of hsp70. In addition, JWA, hsp70, hsp27, and p53 were overexpressed and the expression patterns of JWA, hsp70, and p53 were similar during cell apoptosis. H2O2 led to the cleavage and activation of procaspase-3. In conclusion, these results suggested that JWA might be an effective environmental responsive gene that functions as a parallel with hsp70 in oxidative stress-responsive pathways in K562 cells. Like hsp70, JWA might enhance intracellular defenses and function against H2O2-induced oxidative stress in leukemia cells. At the same time, JWA was involved in the p53-associated signal pathways of oxidative stress-induced apoptosis, which is also caspase-3 dependent.
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PMID:JWA as a novel molecule involved in oxidative stress-associated signal pathway in myelogenous leukemia cells. 1676 76

Arsenic is a ubiquitous environmental contaminant associated with increased risks of human cancers of the skin, lung, bladder, and prostate. Intriguingly, it is also used to treat certain types of leukemia. It has recently been suggested that these paradoxic effects may be mediated by arsenic's ability to simultaneously activate DNA damage and apoptotic and transformation pathways. Here, we investigate the effects of arsenic exposure on the induction of the growth arrest and DNA damage protein 45 alpha (GADD45 alpha), which is thought to play roles in apoptosis, DNA damage response, and cell cycle arrest. We found that arsenic transcriptionally activates the gadd45 alpha promoter located in a 153-bp region between -234 and -81, relative to the transcriptional start site. In addition, this transcriptional induction was abrogated in the presence of H2O2 scavengers, suggesting a role for H2O2 in the transcriptional control of the gadd45a gene through a Fenton-like free radical mechanism.
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PMID:As(III) transcriptionally activates the gadd45a gene via the formation of H2O2. 1681 9

Cobalt octa-4,5-carboxyphthalocyanine propylenglycol ether proposed for antitumor therapy potentiates the cytotoxic effect of ascorbate on HL-60 human leukemia cells. Combination of these substances caused the formation of H2O2 in the medium and initiated apoptotic death of cells. Catalase abolished the cytotoxic effect of this combination. The results indicate that binary catalytic system of this combination can be regarded as a potential antitumor agent.
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PMID:Apoptotic death of human lympholeukemia HL-60 cells resultant from combined effect of cobalt octa-4,5-carboxyphthalocyanine propylenglycol ether and ascorbate. 1684 38

In leukemic cells, glucose transport is activated by SCF and H2O2 through a common signal cascade involving Akt, PLCgamma, Syk, and the Src family, in this order. An explanation can be provided by the phosphorylation of c-kit, the SCF receptor, elicited by either SCF or H2O2. Moreover, antioxidants prevent the SCF effect on glucose transport, confirming the involvement of H2O2 in the pathway leading to glucose-transport activation and suggesting a potential role for reactive oxygen species in leukemia proliferation.
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PMID:Glucose-transport regulation in leukemic cells: how can H2O2 mimic stem cell factor effects? 1711 33

We have previously shown that the anticancer agent doxorubicin undergoes oxidation and inactivation when exposed to myeloperoxidase-containing human leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen peroxide and nitrite. In the current study we report that commercial fetal bovine serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and that nitrite accelerates this oxidation. The efficacy of inactivation was dependent on the concentration of serum present; no reaction was observed when hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a peroxidase in the sera from several suppliers. The peroxidative activity was contained in the >10000 MW fraction. We also found that hemoglobin, a heme protein likely to be present in commercial FBS, is capable of oxidizing doxorubicin in the presence of hydrogen peroxide and that nitrite further stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate cancer cells. Together, this study shows that (pseudo)peroxidases present in sera catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes the tumoricidal activity of the anthracycline, at least in in vitro settings. Finally, this study also points out that addition of H2O2 to media containing FBS will stimulate peroxidase-type of reactions, which may affect cytotoxic properties of studied compounds.
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PMID:Inactivation of anthracyclines by serum heme proteins. 1749 96

Ethacrynic acid (EA), a glutathione S-transferase inhibitor and diuretic agent, inhibits cell growth and induces apoptosis in cancer cells. To improve the activities, the structure of EA has been modified, and it has been shown that EA esters had an increased cell growth inhibitory ability compared with nonesterified analogue. EA butyl-ester (EABE) was synthesized, and its apoptosis induction ability was studied. The efficacy of EABE was compared with that of EA, and the mechanisms of action were studied in HL-60 leukemia cells. EABE exhibited greater cell growth inhibitory and apoptosis induction abilities than did EA. EABE-induced apoptosis in HL-60 cells correlated with increased levels of reactive oxygen species, the death receptor 5 (DR5), and caspase activation and decreased levels of the mitochondrial membrane potential. Pretreatment with antioxidants, either N-acetylcysteine or catalase, completely blocked EABE-induced apoptosis, H2O2 accumulation, and up-regulation of DR5 levels. RG19, a subclone of Raji cells stably transfected with a GSTpi expression vector, and K562 cells with high endogenous GSTP1-1 activity were less sensitive to EABE-induced apoptosis. EABE was more rapidly taken up than EA by HL-60 cells as determined by high-performance liquid chromatography (HPLC) measurements of intracellular concentrations. These results suggest that (a) H2O2 production is a mediator of EABE and EA-induced apoptosis; (b) GSTP1-1 plays a negative role in EABE and EA-induced apoptosis; and (c) the activity of EABE is greater than EA due to its more rapid entry into cells.
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PMID:Ethacrynic acid butyl-ester induces apoptosis in leukemia cells through a hydrogen peroxide mediated pathway independent of glutathione S-transferase P1-1 inhibition. 1769 92

Mimosine, a non-protein amino acid, is mainly known for its action as a reversible inhibitor of DNA replication and, therefore, has been widely used as a cell cycle synchronizing agent. Recently, it has been shown that mimosine also induces apoptosis, as mainly reflected in its ability to elicit characteristic nuclear changes. The present study elucidates the mechanism underlying mimosine's apoptotic effects, using the U-937 leukemia cell line. We now demonstrate that in isolated rat liver mitochondria, mimosine induces mitochondrial swelling that can be inhibited by cyclosporine A, indicative of permeability transition (PT) mega-channel opening. Mimosine-induced apoptosis was accompanied by formation of hydrogen peroxide and a decrease in reduced glutathione levels. The apoptotic process was partially inhibited by cyclosporine A and substantially blocked by the antioxidant N-acetylcysteine, suggesting an essential role for reactive oxygen species formation during the apoptotic processes. The apoptosis induced by mimosine was also accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase 3 and 9 activation. Our results thus imply that mimosine activates apoptosis through mitochondrial activation and formation of H2O2, both of which play functional roles in the induction of cell death.
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PMID:A molecular mechanism for mimosine-induced apoptosis involving oxidative stress and mitochondrial activation. 1805 36

Three novel stable Pt(III) complexes with distorted octahedral structure and (dz2)1 ground state have been obtained in the course of Pt(II)-hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) interaction in alkaline aqueous medium and aerobic conditions. A redox interaction also takes place together with the complexation process leading to the formation of Pt(III) species and organic radicals. The processes in the reaction system and the structure of the complexes formed cis-[Pt(III)(NH3)2(Hp-3H)(H2O)2]H2O1, [Pt(III)(Hp-3H)(H2O)2]H2O2, and [Pt((O,O)Hp-2H)Cl(H2O)3] 3, were studied by UV-Vis, IR, EPR and XPS spectra, thermal (TGS, DSC), potentiometric and magnetic methods. The newly synthesized complexes show promising cytotoxic activity comparable with that of cis-platin in in vitro tests against a panel of human leukemia cell lines. The observed cytotoxicity of the complex 2 against SKW-3 cells (KE-37 derivative) is due to induction of cell death through apoptosis.
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PMID:Synthesis, Structural Characterization, and Cytotoxic Activity of Novel Paramagnetic Platinum Hematoporphyrin IX Complexes: Potent Antitumor Agents. 1830 70

Peroxiredoxins (Prxs) play an important role against various oxidative stresses and intra-cellular signal transduction. Peroxiredoxin 6 (PrxVI) was identified from the disk abalone Haliotis discus discus cDNA library and named HdPrxVI. The full length cDNA of HdPrxVI was 1457 bp with a 654 bp open reading frame (ORF) encoding 218 amino acids. The predicted molecular mass and estimated isoelectric point (pI) of HdPrxVI were 24 kDa and 7.3, respectively. The deduced amino acid sequence demonstrated the greatest degree (72.4%) of identity with Crassostrea gigas PrxVI. The conserved peroxidase catalytic center (42PVCTTE47) with a conserved cysteine residue (Cys44) and a catalytic center for PLA2 activity (27GGSWA31) were observed in the sequence, indicating that it is a member of 1-Cys Prx. Real time PCR results revealed that HdPrxVI mRNA is constitutively expressed in all tissues in a tissue-specific manner. During exposure to haemorrhagic septicaemia virus (VHSV), HdPrxVI mRNA transcription was down-regulated in the gill, suggesting that the abalone responded to the viral infection quickly, and HdPrxVI played a physiological role against virus-induced oxidative stress. The purified recombinant HdPrxVI, together with dithiothreitol (DTT), was shown to scavenge H2O2 in human leukemia THP-1 cells and provided protection against H2O2-induced apoptosis.
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PMID:Molecular cloning, characterization and expression analysis of peroxiredoxin 6 from disk abalone Haliotis discus discus and the antioxidant activity of its recombinant protein. 1946 Apr 42

Although the first reactive oxygen species (ROS) formed during irradiation of photosensitized cells is almost invariably singlet molecular oxygen (1O2), other ROS have been implicated in the phototoxic effects of photodynamic therapy (PDT). Among these are superoxide anion radical (*O2(-)), hydrogen peroxide (H2O2) and hydroxyl radical (*OH). In this study, we investigated the role of H2O2 in the pro-apoptotic response to PDT in murine leukemia P388 cells. A primary route for detoxification of cellular H2O2 involves the peroxisomal enzyme catalase. Inhibition of catalase activity by 3-amino-1,2,4-triazole led to an increased apoptotic response. PDT-induced apoptosis was impaired by addition of an exogenous recombinant catalase analog (CAT-skl) that was specifically designed to enter cells and more efficiently localize in peroxisomes. A similar effect was observed upon addition of 2,2'-bipyridine, a reagent that can chelate Fe+2, a co-factor in the Fenton reaction that results in the conversion of H2O2 to *OH. These results provide evidence that formation of H2O2 during irradiation of photosensitized cells contributes to PDT efficacy.
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PMID:A role for hydrogen peroxide in the pro-apoptotic effects of photodynamic therapy. 1965 20


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