Keywords: Glutathione, Melphalan, Nitric Oxide, Nitric Oxide Donor, Animal Cell, Antineoplastic Activity, Article, Breast Cancer, Cancer Cell Culture, Cell Cycle, Cell Strain Mcf 7, Cell Strain V 79, Cell Survival, Clonogenic Assay, Controlled Study, Drug Cytotoxicity, Drug Sensitivity, Drug Uptake, Human, Human Cell, Lung Fibroblast, Nonhuman, Priority Journal, Buthionine Sulfoximine, Cricetinae, Dna Repair, Drug Synergism, Tumor Cells,
Affiliations: Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, United States
Univ. of New Mexico Cancer Center, Albuquerque, NM 87131, United States
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Wink, D.A., Hanbauer, I., Krishna, M.C., Degraff, W., Gamson, J., Mitchell, J.B., Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species (1993) Proc Natl Acad Sci USA, 90, pp. 9813-9817
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Wink, D.A., Cook, J.A., Krishna, M.C., Hanbauer, I., Degraff, W., Gamson, J., Mitchell, J.B., Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: Further insights into the role nitric oxide plays in oxidative stress (1995) Arch Biochem Biophys, 319, pp. 402-407
Cook, J. A., Iype, S. N., Mitchell, J. B., Differential specificity of monochlorobimane for isozymes of human and rodent glutathione-S-transferases (1991) Cancer Res, 51, pp. 1606-1612
Cook, J. A., Kim, S. A., Krishna, M. C., Pacelli, R., Mitchell, J. B., Vodovotz, Y., Nims, R. W., Wink, D. A., Convenient colorimetric and fluorimetric assays for S-nitrosothiols (1996) Anal Biochem, 238, pp. 150-158
Fast, D. J., Lynch, R. C., Leu, R. W., Nitric oxide production by tumor targets in response to TNF: Paradoxical correlation with susceptibility to TNF-mediated cytotoxicity without direct involvement in the cytotoxic mechanism (1992) J Leukoc Biol, 52, pp. 255-261
Fienstein, D. L., Galea, E., Roberts, S., Berquist, H., Wang, H., Reis, D. J., Induction of nitric oxide synthase in rat C6 glioma cells (1994) J Neurochem, 62, pp. 315-321
Green, J. A., Vistica, D. T., Young, R. C., Hamilton, T. C., Rogan, A. M., Ozols, R. F., Potentiation of melphalan cytotoxicity in human ovarian cancer cell lines by glutathione depletion (1984) Cancer Res, 44, pp. 5427-5431
Hamilton, T. C., Winker, M. A., Louie, K. G., Batist, G., Behrens, B. C., Tsuruo, T., Grotzinger, K. R., Ozols, R. F., Augmentation of adriamycin, melphalan, and cisplatin cytotoxicity in drug-resistant and -sensitive human ovarian cancer cell lines by buthionine sulfoximine mediated glutathione depletion (1985) Biochem Pharmacol, 34, pp. 2583-2586
Hibbs, J. B., Vavrin, Z., Taintor, R. R., L-arginine is required for the expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells (1987) J Immunol, 138, pp. 550-565
Kramer, R. A., Greene, K., Ahmad, S., Vistica, D. T., Chemosensitization of L-phenylalanine mustard by the thiol-modulating agent buthionine sulfoximine (1987) Cancer Res, 47, pp. 1593-1597
Kroncke, K. -D., Fechsel, K., Schmidt, T., Zenke, F. T., Dasting, I., Wesener, J. R., Bettermann, H., Kolb-Bachofen, V., Nitric oxide destroys zinc-finger clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9 (1994) Biochem Biophys Res Commun, 200, pp. 1105-1110
Maragos, C. M., Morley, D., Wink, D. A., Dunams, T. M., Saavedra, J. E., Hoffman, A., Bove, A. A., Keefer, L. K., Complexes of NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects (1991) J Med Chem, 34, pp. 3242-3247
Meyn, R. E., Murray, D., Cell cycle effects of alkylating agents (1986) Cell Cycle Effects of Drugs, pp. 170-188. , Dethlefsen LA (ed.), Pergamon Press: New York
Misra, R. R., Hochadel, J. F., Smith, G. T., Waalkes, M. P., Wink, D. A., Evidence that nitric oxide enhances cadmium toxicity by displacing the metals from metallothionein (1995) Chem Res Toxicol, 9, pp. 326-332
Mitchell, J. B., Wink, D. A., Degralf, W., Gamson, J., Keefer, L. K., Krishna, M. C., Hypoxic mammalian cell radiosensitization by nitric oxide (1993) Cancer Res, 53, pp. 5845-5848
O'Dwyer, P. J., Hamilton, T. C., Lacreta, F. P., Gallo, J. M., Kilpatrick, D., Halbherr, T., Brennan, J., Ozols, R. F., Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer (1996) J Clin Oncol, 14, pp. 249-256
Ozols, R. F., Louie, K. G., Plowman, J., Behrens, B. C., Fine, R. L., Dykes, D., Hamilton, T. C., Enhanced melphalan toxicity in human ovarian cancer in vitro and in tumor-bearing nude mice by buthionine sulfoximine depletion of glutathione (1987) Biochem Pharm, 36, pp. 147-153
Robbins, R. A., Barnes, B. J., Springall, D. R., Warren, J. B., Kwon, O. J., Buttery, L. D. K., Wilson, A. J., Polak, J. M., Expression of inducible nitric oxide in human lung epithelial cells (1994) Biochem Biophys Res Commun, 203, pp. 209-218
Schwarz, M. A., Lazo, J. S., Yalowich, J. C., Allen, W. P., Whitmore, M., Bergonia, H. A., Tzeng, E., Pitt, B. R., Metallothionein protects against the cytotoxic and DNA-dumaging effects of nitric oxide (1995) Proc Natl Acad Sci USA, 9, pp. 4452-4456
Skapek, S. X., Colvin, O. M., Griffith, O. W., Elion, G. B., Bigner, D. D., Friedman, H. S., Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice (1988) Cancer Res, 48, pp. 2764-2767
Stuehr, D. J., Nathan, C. F., A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells (1989) J Exp Med, 169, pp. 1543-1555
Thomsen, L. L., Lawton, F. G., Knowles, R. G., Beesley, J. E., Riveros-Moreno, V., Moncada, S., Nitric oxide synthase activity in human gynecological cancer (1994) Cancer Res, 54, pp. 1352-1357
Walker, M. W., Kinter, M. T., Roberts, R. J., Spitz, D. R., Nitric oxide-induced cytotoxicity: Involvement of cellular resistance to oxidative stress and the role of glutathione in protection (1995) Pediat Res, 37, pp. 41-47
Wink, D. A., Hanbauer, I., Krishna, M. C., Degraff, W., Gamson, J., Mitchell, J. B., Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species (1993) Proc Natl Acad Sci USA, 90, pp. 9813-9817
Wink, D. A., Laval, J., The Fpg protein, a DNA repair enzyme, is inhibited by the biomediator nitric oxide in vitro and in vivo (1994) Carcinogenesis, 15, pp. 2125-2129
Wink, D. A., Nims, R. W., Darbyshire, J. F., Christodoulou, D., Hanbauer, I., Cox, G. W., Laval, F., Mitchell, J. B., Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction (1994) Chem Res Toxicol, 7, pp. 519-525
Wink, D. A., Christodoulou, D., Ho, M., Krishna, M. C., Cook, J. A., Haul, H., Randolph, J. K., Meyer, T., A discussion of electrochemical techniques for the detection of nitric oxide (1995) Methods: A Companion to Methods in Enzymology, 7, pp. 71-77
Wink, D. A., Cook, J. A., Krishna, M. C., Hanbauer, I., Degraff, W., Gamson, J., Mitchell, J. B., Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: Further insights into the role nitric oxide plays in oxidative stress (1995) Arch Biochem Biophys, 319, pp. 402-407
Nitric oxide enhancement of melphalan-induced cytotoxicity
The effects of the diatomic radical, nitric oxide (NO), on melphalan-induced cytotoxicity in Chinese hamster V79 and human MCF-7 breast cancer cells were studied using clonogenic assays. NO delivered by the NO-releasing agent (C2H5)2N[N(O)NO]-Na+ (DEA/NO; 1 mM) resulted in enhancement of melphalan-mediated toxicity in Chinese hamster V79 lung fibroblasts and human breast cancer (MCF-7) cells by 3.6- and 4.3-fold, respectively, at the IC50 level. Nitrite/nitrate and diethylamine, the ultimate end products of DEA/NO decomposition, had little effect on melphalan cytotoxicity which suggests that NO was responsible for the sensitization. Whereas maximal sensitization of melphalan cytotoxicity by DEA/NO was observed for simultaneous exposure of DEA/NO and melphalan, cells pretreated with DEA/NO were sensitized to melphalan for several hours after NO exposure. Reversing the order of treatment also resulted in a time-dependent enhancement in melphalan cytotoxicity. To explore possible mechanisms of NO enhancement of melphalan cytotoxicity, the effects of DEA/NO on three factors that might influence melphalan toxicity were examined, namely NO-mediated cell cycle perturbations, intracellular g]utathione (GSH) levels and melphalan uptake. NO pretreatment resulted in a delayed entry into S phase and a G2/M block for both V79 and MCF-7 cells; however, cell cycle redistribution for V79 cells occurred after the cells returned to a level of cell survival, consistent with treatment with melphalan alone. After 15 min exposure of V79 cells to DEA/NO (1 mM), GSH levels were reduced to 40% of control values; however, GSH levels recovered fully after 1 h and were elevated 2 h after DEA/NO incubation. In contrast, DEA/NO (1 mM) incubation did not reduce GSH levels significantly in MCF-7 cells (approximately 10%). Melphalan uptake was increased by 33% after DEA/NO exposure in V79 cells. From these results enhancement of melphalan cytotoxicity mediated by NO appears to be complex and may involve several pathways, including possibly alteration of the repair of melphalan-induced lesions. Our observations may give insights for improving tumour kill with melphalan using either exogenous or possibly endogenous sources of NO.
Nitric oxide enhancement of melphalan-induced cytotoxicity
No results.
Nitric oxide enhancement of melphalan-induced cytotoxicity
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