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Chemical Compound Review

BUTHIONINE SULFOXIMINE     2-amino-4- (butylsulfonimidoyl)butanoic acid

Synonyms: AG-F-70777, CHEMBL1627290, BSPBio_002464, B2640_SIGMA, CHEBI:28714, ...
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High impact information on BUTHIONINE SULFOXIMINE

  • Glutathione deficiency in newborn rats, produced by administration of L-buthionine-(S,R)-sulfoximine, a transition-state inactivator of gamma-glutamylcysteine synthetase, decreases ascorbate levels of kidney, liver, brain, and lung [7].
  • Diamide plus BSO-induced thiol/disulfide imbalance was associated with a biphasic increase in neutrophil adhesion to HUVECs with peak responses observed at 15 minutes (phase 1) and 240 minutes (phase 2) [2].
  • Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-kappaB and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts [8].
  • For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2 [9].
  • BLM and BSO-induced nigral apoptosis was blocked by inhibitors for caspase-3 or c-Jun/AP-1 [10].

Chemical compound and disease context of BUTHIONINE SULFOXIMINE


Biological context of BUTHIONINE SULFOXIMINE


Anatomical context of BUTHIONINE SULFOXIMINE


Associations of BUTHIONINE SULFOXIMINE with other chemical compounds



  • The protective effects of Nrf2 against CYP2E1-dependent toxicity can be blocked by l-buthionine-(S,R)-sulfoximine, a specific inhibitor of glutamate-cysteine ligase, which is a rate-limiting enzyme in the synthesis of GSH and is regulated by Nrf2 [17].
  • Buthionine-sulfoximine (BSO), which reduces the GSH content, not only increased the As2O3 sensitivity but also conquered the MRP1-related cross resistance in HL60/AD [29].
  • Combined addition of VEGF and L-buthionine sulfoximine, a GSH synthesis inhibitor, reversed both GSH levels and the protective effect of VEGF on Ox-LDL-induced cytotoxicity [30].
  • Treatment of control cells with L-buthionine sulfoximine decreases GSH to levels of c-Myc low expressing cells, but it does not modify the growth kinetic of the cells [31].
  • Thus, depletion of thiol antioxidants by BSO, like ovariectomy, causes bone loss through TNFalpha signaling [32].

Analytical, diagnostic and therapeutic context of BUTHIONINE SULFOXIMINE


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  3. Potentiation of melphalan cytotoxicity in human ovarian cancer cell lines by glutathione depletion. Green, J.A., Vistica, D.T., Young, R.C., Hamilton, T.C., Rogan, A.M., Ozols, R.F. Cancer Res. (1984) [Pubmed]
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  7. Glutathione deficiency decreases tissue ascorbate levels in newborn rats: ascorbate spares glutathione and protects. Mãrtensson, J., Meister, A., Mrtensson, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  8. Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors. Huh, Y.J., Kim, J.M., Kim, H., Song, H., So, H., Lee, S.Y., Kwon, S.B., Kim, H.J., Kim, H.H., Lee, S.H., Choi, Y., Chung, S.C., Jeong, D.W., Min, B.M. Cell Death Differ. (2006) [Pubmed]
  9. Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice. Goldring, C.E., Kitteringham, N.R., Elsby, R., Randle, L.E., Clement, Y.N., Williams, D.P., McMahon, M., Hayes, J.D., Itoh, K., Yamamoto, M., Park, B.K. Hepatology (2004) [Pubmed]
  10. Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons. Sawada, H., Ibi, M., Kihara, T., Urushitani, M., Honda, K., Nakanishi, M., Akaike, A., Shimohama, S. FASEB J. (2000) [Pubmed]
  11. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. Khanna, S., Roy, S., Ryu, H., Bahadduri, P., Swaan, P.W., Ratan, R.R., Sen, C.K. J. Biol. Chem. (2003) [Pubmed]
  12. Rapid deterioration of lens fibers in GSH-depleted mouse pups. Calvin, H.I., Medvedovsky, C., David, J.C., Broglio, T.M., Hess, J.L., Fu, S.C., Worgul, B.V. Invest. Ophthalmol. Vis. Sci. (1991) [Pubmed]
  13. Contribution of calpain Lp82-induced proteolysis to experimental cataractogenesis in mice. Nakamura, Y., Fukiage, C., Shih, M., Ma, H., David, L.L., Azuma, M., Shearer, T.R. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  14. Effect of L-buthionine-(S,R)-sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure. Cuzzocrea, S., Zingarelli, B., O'Connor, M., Salzman, A.L., Szabó, C. Br. J. Pharmacol. (1998) [Pubmed]
  15. Characterization of a CHO cell line resistant to killing by the hypoxic cell cytotoxin SR 4233. Giaccia, A.J., Biedermann, K.A., Tosto, L.M., Minchinton, A.I., Kovacs, M.S., Brown, J.M. Int. J. Radiat. Oncol. Biol. Phys. (1992) [Pubmed]
  16. Role of oxyradicals in mutagenicity and DNA damage induced by crocidolite asbestos in mammalian cells. Xu, A., Wu, L.J., Santella, R.M., Hei, T.K. Cancer Res. (1999) [Pubmed]
  17. Transcription factor Nrf2 protects HepG2 cells against CYP2E1 plus arachidonic acid-dependent toxicity. Gong, P., Cederbaum, A.I. J. Biol. Chem. (2006) [Pubmed]
  18. Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2. Yim, C.Y., Hibbs, J.B., McGregor, J.R., Galinsky, R.E., Samlowski, W.E. J. Immunol. (1994) [Pubmed]
  19. Down-regulation of intrinsic P-glycoprotein expression in multicellular prostate tumor spheroids by reactive oxygen species. Wartenberg, M., Ling, F.C., Schallenberg, M., Bäumer, A.T., Petrat, K., Hescheler, J., Sauer, H. J. Biol. Chem. (2001) [Pubmed]
  20. Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. Ogihara, T., Asano, T., Katagiri, H., Sakoda, H., Anai, M., Shojima, N., Ono, H., Fujishiro, M., Kushiyama, A., Fukushima, Y., Kikuchi, M., Noguchi, N., Aburatani, H., Gotoh, Y., Komuro, I., Fujita, T. Diabetologia (2004) [Pubmed]
  21. Glutathione depletion as a determinant of sensitivity of human leukemia cells to cyclophosphamide. Crook, T.R., Souhami, R.L., Whyman, G.D., McLean, A.E. Cancer Res. (1986) [Pubmed]
  22. Requirement of thiol compounds as reducing agents for IL-2-mediated induction of LAK activity and proliferation of human NK cells. Yamauchi, A., Bloom, E.T. J. Immunol. (1993) [Pubmed]
  23. Resolution, detection, and characterization of redox conformers of human HSF1. Manalo, D.J., Liu, A.Y. J. Biol. Chem. (2001) [Pubmed]
  24. Time-dependent pharmacodynamic models in cancer chemotherapy: population pharmacodynamic model for glutathione depletion following modulation by buthionine sulfoximine (BSO) in a Phase I trial of melphalan and BSO. Gallo, J.M., Brennan, J., Hamilton, T.C., Halbherr, T., Laub, P.B., Ozols, R.F., O'Dwyer, P.J. Cancer Res. (1995) [Pubmed]
  25. Effects of L-phenylalanine mustard and L-buthionine sulfoximine on murine and human hematopoietic progenitor cells in vitro. Du, D.L., Volpe, D.A., Grieshaber, C.K., Murphy, M.J. Cancer Res. (1990) [Pubmed]
  26. Oxidative stress-mediated apoptosis. The anticancer effect of the sesquiterpene lactone parthenolide. Wen, J., You, K.R., Lee, S.Y., Song, C.H., Kim, D.G. J. Biol. Chem. (2002) [Pubmed]
  27. Role of glutaredoxin in metabolic oxidative stress. Glutaredoxin as a sensor of oxidative stress mediated by H2O2. Song, J.J., Rhee, J.G., Suntharalingam, M., Walsh, S.A., Spitz, D.R., Lee, Y.J. J. Biol. Chem. (2002) [Pubmed]
  28. Heme oxygenase-1 protects HepG2 cells against cytochrome P450 2E1-dependent toxicity. Gong, P., Cederbaum, A.I., Nieto, N. Free Radic. Biol. Med. (2004) [Pubmed]
  29. Arsenic trioxide circumvents multidrug resistance based on different mechanisms in human leukemia cell lines. Seo, T., Urasaki, Y., Takemura, H., Ueda, T. Anticancer Res. (2005) [Pubmed]
  30. VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor. Kuzuya, M., Ramos, M.A., Kanda, S., Koike, T., Asai, T., Maeda, K., Shitara, K., Shibuya, M., Iguchi, A. Arterioscler. Thromb. Vasc. Biol. (2001) [Pubmed]
  31. Inhibition of c-Myc oncoprotein limits the growth of human melanoma cells by inducing cellular crisis. Biroccio, A., Amodei, S., Antonelli, A., Benassi, B., Zupi, G. J. Biol. Chem. (2003) [Pubmed]
  32. Tumor necrosis factor-alpha mediates osteopenia caused by depletion of antioxidants. Jagger, C.J., Lean, J.M., Davies, J.T., Chambers, T.J. Endocrinology (2005) [Pubmed]
  33. Heterogeneity of cellular glutathione among cells derived from a murine fibrosarcoma or a human renal cell carcinoma detected by flow cytometric analysis. Shrieve, D.C., Bump, E.A., Rice, G.C. J. Biol. Chem. (1988) [Pubmed]
  34. Lazaroid treatment prevents death of cultured rat embryonic mesencephalic neurons following glutathione depletion. Grasbon-Frodl, E.M., Andersson, A., Brundin, P. J. Neurochem. (1996) [Pubmed]
  35. The toxic effects, GSH depletion and radiosensitivity by BSO on retinoblastoma. Yi, X., Ding, L., Jin, Y., Ni, C., Wang, W. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
  36. In vivo therapeutic potential of combination thiol depletion and alkylating chemotherapy. Siemann, D.W., Beyers, K.L. Br. J. Cancer (1993) [Pubmed]
  37. Overproduction of Cu/Zn-superoxide dismutase or Bcl-2 prevents the brain mitochondrial respiratory dysfunction induced by glutathione depletion. Mérad-Saïdoune, M., Boitier, E., Nicole, A., Marsac, C., Martinou, J.C., Sola, B., Sinet, P.M., Ceballos-Picot, I. Exp. Neurol. (1999) [Pubmed]
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