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K Harada - One of the best experts on this subject based on the ideXlab platform.
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Enhancement by hyperthermia of the in vivo antitumour effect of doxorubicin hydrochloride (DOX) and Buthionine Sulfoximine (BSO)-hydroxyapatite (HAP) complex.
International journal of oncology, 1997Co-Authors: M Imamura, Toshihito Seki, K Kunieda, K Inoue, T Tamai, Akira Nishimura, K HaradaAbstract:We have developed a new type of drug delivery system (DDS) comprising a complex of porous hydroxyapatite (HAP) with the anticancer drug doxorubicin hydrochloride (DOX) and the glutathione inhibitor Buthionine Sulfoximine (BSO) (DOX and BSO-HAP complex). We then studied the antitumour effect of DOX and BSO-HAP combined with 44 degrees C hyperthermia for 40 min. It was found that in mice this combined treatment suppressed the growth of sarcoma 180 in terms of tumour volume to 36% in comparison viith mice given plain HAP, and was more effective than HAP + hyperthermia or DOX- and BSO-HAP. These results were also confirmed by histological observation.
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Antitumor effects of Doxorubicin hydrochloride (dox) and Buthionine Sulfoximine (bso)-hydroxyapatite (hap) complex on transplanted tumors in-vivo.
Oncology reports, 1995Co-Authors: M Imamura, Toshihito Seki, K Kunieda, Masayuki Wakabayashi, K Inoue, Y Obiya, K HaradaAbstract:We prepared hydroxyapatite (HAP) beads containing doxorubicin hydrochloride (DOX) and Buthionine Sulfoximine (BSO), as a DOX and BSO-HAP complex. When the complex was implanted into mice bearing sarcoma 180 tumor, the antitumor effect of the complex was intensified 1.5-fold, as assessed using tumor volume, on day 27 as compared with that of a complex of DOX-HAP only. Therefore, we concluded that the antitumor effect of the DOX and BSO-HAP complex was increased through depletion of the intracellular radical scavenger glutathione (GSH) by released BSO and subsequently free radicals produced by released DOX.
Lester Packer - One of the best experts on this subject based on the ideXlab platform.
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Stereospecific Effects of R-Lipoic Acid on Buthionine Sulfoximine-Induced Cataract Formation in Newborn Rats
Biochemical and biophysical research communications, 1996Co-Authors: Indrani Maitra, Elena Serbinova, Hans J. Tritschler, Lester PackerAbstract:Abstract This study revealed a marked stereospecificity in the prevention of Buthionine Sulfoximine-induced cataract, and in the protection of lens antioxidants, in newborn rats by α-lipoate. R- and racemic α-lipoate decreased cataract formation from 100% (Buthionine Sulfoximine only) to 55% (Buthionine Sulfoximine + R-α-lipoic acid) and 40% (Buthionine Sulfoximine + rac-α-lipoic acid) (p
Emma Saavedra - One of the best experts on this subject based on the ideXlab platform.
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Buthionine Sulfoximine is a multitarget inhibitor of trypanothione synthesis in Trypanosoma cruzi.
FEBS letters, 2017Co-Authors: Citlali Vázquez, Marlen Mejia-tlachi, Zabdi González-chávez, Aketzalli Silva, José S. Rodríguez-zavala, Rafael Moreno-sánchez, Emma SaavedraAbstract:Buthionine Sulfoximine (BSO) induces decreased GSH and trypanothione [T(SH)2] pools in trypanosomatids, presumably because only gamma-glutamylcysteine synthetase (γECS) is blocked. However, some BSO effects cannot be explained by exclusive γECS inhibition; therefore, its effect on the T(SH)2-metabolism pathway in Trypanosoma cruzi was re-examined. Parasites exposed to BSO did not synthesize T(SH)2 even when supplemented with cysteine or glutathione, suggesting trypanothione synthetase (TryS) inhibition by BSO. Indeed, recombinant γECS and TryS, but not glutathione synthetase, were inhibited by BSO and kinetics and docking analyses on a TcTryS 3D model suggested BSO binding at the glutathione site. Furthermore, parasites overexpressing γECS and TryS showed ~50% decreased activities after BSO treatment. These results indicated that BSO is also an inhibitor of TryS. This article is protected by copyright. All rights reserved.
Maciej Stępnik - One of the best experts on this subject based on the ideXlab platform.
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Potentiation of arsenic trioxide cytotoxicity by Parthenolide and Buthionine Sulfoximine in murine and human leukemic cells
Cancer Chemotherapy and Pharmacology, 2008Co-Authors: Markus Duechler, Małgorzata Stańczyk, Małgorzata Czyż, Maciej StępnikAbstract:Purpose To possibly increase the in vitro cytotoxic activity of arsenic trioxide (ATO) by combining it with Parthenolide (PRT), a known NF-κB inhibitor and Buthionine Sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase. Methods Several cell lines representing various hematological malignancies were treated in vitro with the study drugs alone or in combinations. Flow cytometry was used to assess cell death rates and reative oxygen species production. Glutathione and ATP levels were determinded using a photometric and a luminometric assay, respectively. Cell death was characterised by fluorescence microscopy and DNA fragmentation analysis. Results PRT increased cytotoxicity of ATO in seven out of eight cell lines. Addition of Buthionine Sulfoximine (BSO) further potentiated cytotoxicity of the combined treatment. When combined with PRT and BSO, clinically achievable concentrations of ATO (2.5 μM) induced cytotoxicity rates of 80–98% after 24 h. Importantly, lymphocytes from healthy donors were largely unaffected by these treatment modalities, also after growth stimulation in cell culture. N -acetylcysteine inhibited the cytotoxic effects of the triple combination. Treatment of leukemic cells with ATO, PRT and BSO rapidly depleted cells from glutathione, induced oxidative stress and decreased intracellular ATP levels. Cell death showed characteristics of necrosis presumably as a result of ATP loss. Conclusion Based on the observed selectivity towards malignant cells this combination may offer a therapeutic option applicable to different kinds of leukemia.
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Potentiation of arsenic trioxide cytotoxicity by Parthenolide and Buthionine Sulfoximine in murine and human leukemic cells
Cancer chemotherapy and pharmacology, 2007Co-Authors: Markus Duechler, Małgorzata Stańczyk, Malgorzata Czyz, Maciej StępnikAbstract:Purpose To possibly increase the in vitro cytotoxic activity of arsenic trioxide (ATO) by combining it with Parthenolide (PRT), a known NF-κB inhibitor and Buthionine Sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase.
Antonio Morello - One of the best experts on this subject based on the ideXlab platform.
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Effects of Buthionine Sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.
Biological research, 2004Co-Authors: Juan Diego Maya, Andrés Rivadulla Rodríguez, Laura Pino, Adriana Pabón, Jorge Ferreira, Mario Pavani, Yolanda Repetto, Antonio MorelloAbstract:Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas' disease, decreased metallothionein activity by approximately 70%. T. cruzi metallothionein was induced by ZnCl2. Metallothionein from T. cruzi was partially purified and its monobromobimane derivative showed a molecular weight of approximately 10,000 Da by SDS-PAGE analysis. The concentration of trypanothione, the major glutathione conjugate in T. cruzi, ranged from 3.8 to 10.8 nmol/mg protein, depending on the culture phase. The addition of Buthionine Sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. The possible contribution of metallothionein-like proteins to drug resistance in T. cruzi is discussed.
