Abstract
Glutathione depletion by L-buthionine sulfoximine inhibits the growth of Ehrlich mouse mammary carcinoma, R3230Ac rat mammary carcinoma and the PC3 human prostrate carcinoma cells, in vitro Inhibition of growth occurs within the first 24 hours after exposure to the drug. The cell density does not increase over the initial cell density over 7 days. A549 human lung carcinoma and the DU145 human prostrate carcinoma cells show no inhibition of growth under the same treatment conditions. A comparative study of the R3230Ac and A549 cells demonstrated a marked increase in apoptosis following L-BSO treatment in R3230Ac, which was dependent on L-BSO concentration and incubation time. L-BSO did not induce apoptosis in A549 cells at any of the concentrations tested. The incidence of apoptosis for R3230Ac cells following exposure to 0.1 mM L-BSO was similar to the incidence of radiation-induced apoptosis observed after exposure to 10 Gy. Treatment with L-BSO or radiation alone inhibited O2 utilization in of R3230ac, while no effect on O2 utilization was observed in A549 cells. LBSO altered the bioreductive capacity of both the R3230Ac and A549 cells. These results suggest that the ability of L-BSO to block mitochondrial O2 utilization may be involved in the apoptotic response in R3230Ac cells.
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References
Biaglow, J.E., and Varnes, M. The role of thiols in cellular response to radiation and drugs. Radiation Res 1983; 95:437–455.
Biaglow JE, Mitchell JB, Held K. The importance of peroxide and superoxide in the X-ray response. Int J Oncology Biol Phys 1992;22:665–669.
Biaglow, J.E and Varnes. Cellular protection against damage by hydroperoxides: Role of Glutathione. Basic Life Sci 1988;49:567–573.
Tuttle, S.E. and Biaglow, J.E. Sensitivity to chemical oxidants and radiation in CHO lines deficient in oxidative pentose cycle activity. Int. J. Radiat; Oncol Biol. Phys. 1992, 22:671–675.
Puertas Fj, Diaz-Llopis, Chiupoint E, Roma A, Romero FJ. Glutathione system of human retina: enzymatic conjugation of lipid peroxidation products. Free Radic Biol Ned 1993;14:549–551.
Vlachaki MT, Meyn RE. ASTRO research fellowship: the role of BCL-2 and glutathione in an antioxidant pathway to prevent radiation-induced apoptosis. Int J Radiat Oncol Biol Phys 1998;42:185–190.
Mirkovic N, Voehringer DW, Story MD, Mcconkey DJ, Mcdonnell TJ, Meyn RE. Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene 1997;19:1461–1469.
Chibelli L, Fanelli C, Rotilio G, Lafavia E, Coppola S, Colussi C, Civitareeale P, Ciriolo MKR. Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB J 1988:12:479–486.
Slater AF, Stefan C, Nobel I, van den Dobbelsteen DJ, Orrenius S. Signaling mechanisms and oxidative stress in apoptosis. Toxicol Lett 1995;82–83:149–153
Celli A, Que FG, Gores GJ, Larusso NF. Glutathione depletion is associated with decreased Bcl-2 expression and increased apoptosis in cholagiocytes. Am J Physiol 1998;274:G749–757.
Bojes HK, Datta K, Xu J, Chin A, Simonian P, Nunez G, Kehrer JP. Bcl-xL over expression attenuates glutathione depletion in F15.12 cells following interleukin3 withdrawal. Biochem J 1997;325:315–319.
Van den Dobbelsteen DJ, Nobel CSI, Schlegel J, Cotgreave IA, Orrenius S, Slater AF. Rapid and specific efflux of reduced glutathione during apoptosis induced by antiFas/APO-1 antibody. J Biol Chem 1996;26:15420–15427.
Kurihara M, Kurihara H, Tsukuda M. Elevation of cytoplasmic cytochrome c in radiation-induced apoptosis. Jpn J Cancer Res 1998;10:1082–1086.
Wullner U, Seyfried J, Groscurth P, Beinroth S, Winter S, Gleichmann M, Heneka M, Leschmann P, Schulz JB, Weller M, Klockgetherr T. Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function. Brain Res 1999;24: 150–160.
Wan XS, St Clair DK. Differential cytotoxicity of buthionine sulfoximine to “normal” and transformed human lung fibroblasts. Cancer Chemother Pharmacol 1993;33:210220.
Nicole A, Santiard-Baron D, Ceballos-Picot, I. Direct evidence for glutathione as mediator of apoptosis in neuronal cells. Biomed Pharmacother 1988;52:349–355.
Asohiba K, Yasui S, Nishimura K, Nagai A. Thiol depletion induces apoptosis in cultured lung fibroblasts. Am J Respir Cell Mol Biol 1999;21:54–60.
Boggs SE, McCormick TS, Lapetina EG. Glutathione levels determine apoptosis in macrophages. Biochem Biophys Res Commun 1988;247:229–233.
Lizard G, Gueldry S, Sordet O, Monier S, Athias A, Miguet C, Bessede G, Lemaire S, Solary E, Gambert P. Glutathione is implied in the control of 7-ketocholesterol-induced apoptosis, which is associated with radical oxygen species. FASEB J 1998;15:1651–1663.
Varnes ME, Chiu SM, Xue LY, Oleinick NL. Photodynamic therapy-induced apoptosis in lymphoma cells: translocation of cytochrome c causes inhibition of respiration as well as caspase activation. Biochem Biophys Res Commun 1999;255:673–679.
Voet, D. and Voet J.G. Biochemistry (1995). John Wiley & Sons, Inc. New York. Pp. 617–623.
Biaglow, JE. Radiation effects in mammalian cells. In: Radiation Chemistry: Principles and Applications, M. A. J. Rogers and Dr. Farhataziz, Eds., 1987 VGH Publishers, 527–564.
Starke, DW, Chen, YC, Bapna, CP, Lesnefsky, EJ, Mieyal, JJ. Sensitivity of protein sufhydryl repair enzymes to oxidative stress. Free Rad Biol Med 1997; 23:373–384.
Muschel RJ, Bernhard EJ, Graze L, McKenna GW, Koch CJ. Cancer Research, 1995;55:995–998.
Biaglow JB, Tuttle S, Evans S. MIBG inhibits respiration: potential for radio and hypertermic sensitization. Int J Radiat Biol Phys 1998;42:871–876.
Biorad protein assay purchased from Cal Biochem Co.
Biaglow J, Donahue J, Tuttle S, Held K, Mieyal J. A method for measuring disulfide reduction by cultured mammalian cells: role of GSH dependent and GSH independent mechanisms. Analytical Biochemistry 2000, 281.71–85
Dethlefson LA, Biaglow JE, Peck VM, Ridinger DN. Toxic effects if extended glutathione depletion by buthionine sulfoximine on murine mammary carcinoma cells. Int J Radiat Oncol Biol Physics 1986;12:1157–1160.
Dethleson LA, Lehaman CM, Biaglow JE, Peck VM. Toxic effects of acute glutathione depletion by buthionine sulfoximine and dimethylfumarate on murine mammary carcinoma cells. Radiation Res 1988;114:215–224.
Biaglow JE, Iramundi I, Koch, CJ, Donahue J, Mieyal, JJ, Stomato T, Tuttle S Raadiation response of cells during altered protein redox. 2003 Radiation Research in press.
Kang VJ, Emery D., Enger MD. Buthionine sulfoximine induced growth inhibition in human lung carcinoma cells does not correlate with glutathione depletion. Cell Biol Toxicol 1991;7:249–261.
Kang YJ, Enger MD. Glutathione content and growth in A549 human lung carcinoma cells. Exp Cell Res 1990;187:177–179.
Baker MA, Hagner,B. Diamide induced shift in protein and glutathione thiol: disulfide status delays DNA rejoining X-irradiation of human cancer cells. Biochem Biophys Acta 1990;1037: 39–47.
Webb JL. (1966) Enzyme and Metabolic Inhibitors, Vol. 3, pp. 602–656, Academic Press, New York
Powlis G, Gasdaska JR, Baker A. Redox signaling and the control of cell growth and death. (1997) Academic Press, N.Y., 329–359.
Milas L, Saito Y, Hunter N, Milross CG, Mason KA. Therapeutic potential of placitaxel-radiation of a murine ovarian carcinoma. Radiother Oncol 1996;40:163–170.
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Biaglow, J.E. et al. (2003). Glutathione Depletion or Radiation Treatment Alters Respiration and Induces Apoptosis in R3230Ac Mammary Carcinoma. In: Dunn, J.F., Swartz, H.M. (eds) Oxygen Transport to Tissue XXIV. Advances in Experimental Medicine and Biology, vol 530. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0075-9_15
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DOI: https://doi.org/10.1007/978-1-4615-0075-9_15
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