Wyniki wyszukiwania

1

The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: Molecular dynamics simulations

100%

Mazerski J., Martelli S., Borowski E.

Acta Biochimica Polonica

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1998

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tom 45

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nr 1

Intercalative binding of the antitumor drugs ametantrone and mitoxantrone to the dodecamer duplex d(CGCGAGCTCGCG)2 was studied by applying molecular dynamics in water with the GROMOS 87 force field. A number of reasonable binding orientations were tested by short pre-simulations. It was shown that in energetically favorable orientation the anthraquinone chromophore is perpendicular to the direction of inter-base hydrogen bonds. Helically shaped side-chains of the drugs fit to the minor groove. The best orientation obtained in pre-simulations was applied in the main simulations. Small but significant differences were found between structures of intercalation complexes of the two drugs with the dodecamer duplex, the mitoxantrone complex possessing more favorable energy. The molecular nature of interactions responsible for those differences has been discussed.

2

Methylxanthines [caffeine, pentoxifylline and theophylline] decrease the mutagenic effect of daunomycin, doxorubicin and mitoxantrone

84%

Piosik J., Gwizdek-Wisniewska A., Ulanowska K., Ochocinski J., Czyz A., Wegrzyn G.

Acta Biochimica Polonica

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2005

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tom 52

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nr 4

Previously performed experiments showed that methylxanthines, especially caffeine, may protect cells against cytostatic or cytotoxic effects of several aromatic compounds. One of the proposed mechanisms of this protection is based on stacking interactions between π electron systems of polycyclic aromatic molecules. In this work, we demonstrate that caffeine and other methylxanthines - pentoxifylline and theophylline - significantly decrease mutagenicity of the anticancer aromatic drugs daunomycin, doxorubicin and mitoxantrone. The spectrophotometric titration of these aromatic compounds by methylxanthines indicated formation of mixed aggregates. The concentrations of free active forms of the drugs decreased when the concentrations of methylxanthines increased in the mixture. Therefore, likely methylxanthines may play a role of scavengers of the free active forms of daunomycin, doxorubicin and mitoxantrone.

3

A comparison of the in vitro genotoxicity of anticancer drugs idarubicin and mitoxantrone

84%

Blasiak J., Gloc E., Warszawski M.

Acta Biochimica Polonica

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2002

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tom 49

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nr 1

Idarubicin is an anthracycline antibiotic used in cancer therapy. Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity. Using the alkaline comet assay we showed that the drugs at 0.01-10 uM induced DNA damage in normal human lymphocytes. The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001). The cells treated with mitoxantrone at 1 uM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min. Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone. Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones. 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone. Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs. Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation. The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.

4

Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients

67%

Adamczyk-Sowa M., Sowa P., Pierzchala K., Polaniak R., Labuz-Roszak B.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 6

5

Autoimmune versus oligodendrogliopathy: the pathogenesis of multiple sclerosis

67%

Nakahara J., Aiso S., Suzuki N.

Archivum Immunologiae et Therapiae Experimentalis

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2010

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tom 58

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nr 5

325-333

6

Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human prostate cancer cells - in vitro study

67%

Koczurkiewicz P., Podolak I., Wojcik K. A., Galanty A., Madeja Z., Michalik M., Czyz J.

Acta Biochimica Polonica

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2013

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tom 60

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nr 3

Triterpene saponosides are widely distributed plant secondary metabolites characterized by relatively low systemic cytotoxicity and a range of biological activities. These include anti-inflammatory, antimicrobial, vasoprotective and antitumor properties. In particular, the ability of saponins to enhance the cytotoxicity of chemotherapeutic drugs opened perspectives for their application in combined cancer chemotherapy. Here, we used human prostate cancer DU-145 cells as an in vitro model to elucidate the synergy of the interactions between biological activities of an oleanane type 13β,28-epoxy triterpene saponoside (Lclet 4) and mitoxantrone, which is a cytostatic drug commonly used in prostate cancer therapy. No cytotoxic or pro-apoptotic effect of Lclet 4 and mitoxantrone administered at the concentrations between 0.05 and 0.1 µg/ml could be seen. In contrast, cocktails of these agents exerted synergistic pro-apoptotic effects, accompanied by the activation of the caspase 3/7 system. This effect was paralleled by attenuating effects of Lclet 4/mitoxantrone cocktails on the invasive potential, metalloproteinase expression and motility of DU-145 cells. Multifaceted and additive effects of Lclet 4 and mitoxantrone on basic cellular traits crucial for prostate cancer progression indicate that the combined application of both agents at systemically neutral concentrations may provide the basis for new promising strategies of prostate cancer chemotherapy.

7

Mitoxantrone ability to induce premature senescence in human dental pulp stem cells and human dermal fibroblasts

67%

Seifrtova M., Havelek R., Soukup T., Filipova A., Mokry J., Rezacova M.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 2

8

The interaction of daunorubicin and mitoxantrone with the red blood cells of acute myeloid leukemia patients

67%

Marczak A., Wrzesien-Kus A., Krykowski E., Robak T., Jozwiak Z.

Cellular and Molecular Biology Letters

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2003

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tom 08

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nr 4

The effect of DNR and MIT on erythrocyte membrane structure was examined using Electron Spin Resonance spectroscopy and the fluorimetric technique. The results suggest that the in vivo interaction of the drugs with the RBCs of AML patients led to a perturbation in the structure of plasma membrane components. Differences between DNR and MIT were only noted in the interaction of the drugs with deeper regions of the lipid bilayer.

9

Metoclopramide and nitrendipine are unable to enhance cytotoxicity of mitoxantrone in sensitive and resistant murine leukemias in vivo

59%

Potemski P., Polakowski P.

Archivum Immunologiae et Therapiae Experimentalis

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1997

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tom 45

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nr 2-3

Ograniczanie wyników

The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: Molecular dynamics simulations

Methylxanthines [caffeine, pentoxifylline and theophylline] decrease the mutagenic effect of daunomycin, doxorubicin and mitoxantrone

A comparison of the in vitro genotoxicity of anticancer drugs idarubicin and mitoxantrone

Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients

Autoimmune versus oligodendrogliopathy: the pathogenesis of multiple sclerosis

Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human prostate cancer cells - in vitro study

Mitoxantrone ability to induce premature senescence in human dental pulp stem cells and human dermal fibroblasts

The interaction of daunorubicin and mitoxantrone with the red blood cells of acute myeloid leukemia patients

Metoclopramide and nitrendipine are unable to enhance cytotoxicity of mitoxantrone in sensitive and resistant murine leukemias in vivo