Involvement of hydrogen peroxide and hydroxyl radical in chemically induced apoptosis of HL-60 cells

Ikeda, K; Kajiwara, Kouichi; Tanabe, Eiko; Tokumaru, Sadako; Kishida, Etsu; Masuzawa, Yasuo; Kojo, Shosuke

doi:10.1016/s0006-2952(99)00055-6

Cited by 70 publications

(36 citation statements)

References 27 publications

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“…The possibility that necrosis could be due a specific disruption of the respiratory chain may also be discarded, because treatment with oligomycin (which inhibits the mitochondrial F 0 /F 1 -ATPase) in glucose-containing medium only had minor effects on the ATP level (Fig. 7A) (8,11,47). In addition, our results indicate that preincubation with BSO potentiates the trigger of oxidation by all antitumor drugs, as revealed by the increase in H 2 DCFDA-derived fluorescence.…”

Section: Effects Of Exogenous H 2 O 2 -The Results Inmentioning

confidence: 99%

Effect of Glutathione Depletion on Antitumor Drug Toxicity (Apoptosis and Necrosis) in U-937 Human Promonocytic Cells

Troyano¹,

Fernández²,

Sancho³

et al. 2001

Journal of Biological Chemistry

141

101

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Treatment with the DNA topoisomerase inhibitors etoposide, doxorubicin, and camptothecin, and with the alkylating agents cisplatin and melphalan, caused peroxide accumulation and apoptosis in U-937 human promonocytic cells. Preincubation with the reduced glutathione (GSH) synthesis inhibitor L-buthionine-(S,R)-sulfoximine (BSO) always potentiated peroxide accumulation. However, although GSH depletion potentiated the toxicity of cisplatin and melphalan, occasionally switching the mode of death from apoptosis to necrosis, it did not affect the toxicity of the other antitumor drugs. Hypoxia or preincubation with antioxidant agents attenuated death induction, apoptotic and necrotic, by alkylating drugs. The generation of necrosis by cisplatin could not be mimicked by addition of exogenous H 2 O 2 instead of BSO and was not adequately explained by caspase inactivation nor by a selective fall in ATP content. Treatment with cisplatin and melphalan caused a late decrease in mitochondrial transmembrane potential (⌬⌿m), which was much greater during necrosis than during apoptosis. The administration of the antioxidant agents N-acetyl-L-cysteine and butylated hydroxyanisole after pulse treatment with cisplatin or melphalan did not affect apoptosis but attenuated necrosis. Under these conditions, both antioxidants attenuated the necrosis-associated ⌬⌿m decrease. These results indicate that oxidation-mediated alterations in mitochondrial function regulate the selection between apoptosis and necrosis in alkylating drug-treated human promonocytic cells.

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Section: Effects Of Exogenous H 2 O 2 -The Results Inmentioning

confidence: 99%

Effect of Glutathione Depletion on Antitumor Drug Toxicity (Apoptosis and Necrosis) in U-937 Human Promonocytic Cells

Troyano¹,

Fernández²,

Sancho³

et al. 2001

Journal of Biological Chemistry

141

101

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“…When patients were divided according to treatment regimen, the impact of Hb on disease response was greater in the subset treated with epirubicin than in the subgroup receiving CMF. Hypoxia-induced resistance of tumour cells to anthracyclines has been repeatedly described in vitro (Ikeda et al, 1999;Matthews et al, 2001). The generation under normal oxygenation of reactive oxygen species such as hydrogen peroxide and nitric oxide, which cause oxidative damage to cellular proteins and apoptosis, could be a possible mechanism (Ikeda et al, 1999;Matthews et al, 2001).…”

Section: Discussionmentioning

confidence: 98%

“…Hypoxia-induced resistance of tumour cells to anthracyclines has been repeatedly described in vitro (Ikeda et al, 1999;Matthews et al, 2001). The generation under normal oxygenation of reactive oxygen species such as hydrogen peroxide and nitric oxide, which cause oxidative damage to cellular proteins and apoptosis, could be a possible mechanism (Ikeda et al, 1999;Matthews et al, 2001). In addition, in the absence of oxygen, P450 reductase interacts with anthracyclines, leading to cleavage of the anthracycline glycosidic bond and producing a molecule with no antitumour activity (Pan et al, 1981).…”

Section: Discussionmentioning

confidence: 98%

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

et al. 2003

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The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen þ tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage 450% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (Po0.01 and o0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l À1 onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, Po0.05) and 13.0 g/dl À1 (81.0 vs 57.6%, Po0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels p13 g dl À1 showed a lower treatmentinduced reduction in Ki67 expression (Po0.04) and a higher Ki67 expression at postoperative evaluation (Po0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism.

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“…Scavenging of H 2 O 2 caused failure of apoptosis. Reactive oxygen species generation has been demonstrated in a range of tumours 6 -48 h after treatment with various anticancer agents (Ikeda et al, 1999;Huang et al, 2003;Fawcett et al, 2005;Rahmani et al, 2005). Indeed, the antitumour activity of paclitaxel in mice was abolished by NAC as accumulation of H 2 O 2 is an early and crucial step for paclitaxel-induced cancer cell death (Alexandre et al, 2006a).…”

Section: Revised 3 May 2006; Accepted 17 May 2006mentioning

confidence: 99%

Regional localisation of p53-independent apoptosis determines toxicity to 5-fluorouracil and pyrrolidinedithiocarbamate in the murine gut

et al. 2006

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Pyrrolidinedithiocarbamate (PDTC) enhanced the activity of 5-fluorouracil (5-FU) in a colorectal cancer xenograft model. Pyrrolidinedithiocarbamate also reduced gastrointestinal toxicity associated with 5-FU therapy in large but not small bowel. We sought to clarify the basis of this differential enteric toxicity. Apoptosis and mitosis were assessed on a cell positional basis in small and large intestinal crypts of p53 wild-type ( þ / þ ) and p53 null (À/À) mice 6, 12, 24, 36, 48 and 72 h after the administration of high (200 mg kg À1 ) or low (40 mg kg À1 ) dose 5-FU7250 mg kg À1 PDTC. Regimens were chosen to model a single human dose and a weekly schedule. The effects of another antioxidant N-acetylcysteine (NAC) were also investigated. Large intestinal crypts affect apoptosis purely by p53-dependent mechanisms, whereas small intestinal crypts are able to initiate both p53-dependent and -independent pathways following treatment with 5-FU. Pyrrolidinedithiocarbamate and NAC antagonised p53-dependent but potentiated p53-independent apoptotic activity. Consequently, the proportion of surviving clonogens increased in the large but not in the small intestine. Regional availability of p53-dependent and -independent apoptotic pathways in small and large intestine together with separate modulation of these pathways by antioxidants explains the different regional enterotoxicity following 5-FU therapy.

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Involvement of hydrogen peroxide and hydroxyl radical in chemically induced apoptosis of HL-60 cells

Cited by 70 publications

References 27 publications

Effect of Glutathione Depletion on Antitumor Drug Toxicity (Apoptosis and Necrosis) in U-937 Human Promonocytic Cells

Effect of Glutathione Depletion on Antitumor Drug Toxicity (Apoptosis and Necrosis) in U-937 Human Promonocytic Cells

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

Regional localisation of p53-independent apoptosis determines toxicity to 5-fluorouracil and pyrrolidinedithiocarbamate in the murine gut

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