Injuries to cultivated BJA-B cells by ajoene, a garlic-derived natural compound: Cell viability, glutathione metabolism, and pools of acidic amino acids

作者: Klaus Scharfenberg , Thomas Ryll , Roland Wagner , Karl G. Wagner

DOI: 10.1002/JCP.1041580108

关键词:

摘要: Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide), a garlic-derived natural compound, which had been shown to have cytostatic/cytotoxic properties, was tested with B cell lymphoma-derived line (BJA-B cells) in order elucidate its mechanism of cytotoxic action. Viability the cells determined by Trypan blue exclusion test and colorimetric tetrazolium (MTT) assay, whereas metabolic disturbance evaluated measuring pools reduced (GSH), oxidized glutathione (GSSG) acidic amino acids, Glu Asp. Fast uptake ajoene accompanied an immediate reduction CSH increase GSSG levels. The extent these changes, as well further development metabolite pools, depended on dose per cell. At sublethal GSH rose at later stages levels much higher than control experiment. Bleb formation cytoplasmic membrane rapid phenomenon, although injuries detected developed only stage. MTT performed parallel experiment (48 h after addition), showed, however, that viability established very beginning exposure. Altogether, action strongly resembled oxidative stress (i.e., interference SH homeostasis pleiotropic consequences physiology metabolism). © 1994 Wiley-Liss, Inc.

参考文章(28)
J.C. Livesey, D.J. Reed, Measurement of glutathione-protein mixed disulfides International Journal of Radiation Oncology Biology Physics. ,vol. 10, pp. 1507- 1510 ,(1984) , 10.1016/0360-3016(84)90491-7
Eric. Block, Saleem. Ahmad, James L. Catalfamo, Mahendra K. Jain, Rafael. Apitz-Castro, The chemistry of alkyl thiosulfinate esters. 9. Antithrombotic organosulfur compounds from garlic: structural, mechanistic, and synthetic studies Journal of the American Chemical Society. ,vol. 108, pp. 7045- 7055 ,(1986) , 10.1021/JA00282A033
Cyrus M. Dhanbhoora, John R. Babson, Thiol depletion induces lethal cell injury in cultured cardiomyocytes. Archives of Biochemistry and Biophysics. ,vol. 293, pp. 130- 139 ,(1992) , 10.1016/0003-9861(92)90375-7
Karl W. Lanks, Glutamine is responsible for stimulating glycolysis by L929 cells. Journal of Cellular Physiology. ,vol. 126, pp. 319- 321 ,(1986) , 10.1002/JCP.1041260224
Kai Mithöfer, Martha S. Sandy, Martyn T. Smith, Donato Di Monte, Mitochondrial poisons cause depletion of reduced glutathione in isolated hepatocytes Archives of Biochemistry and Biophysics. ,vol. 295, pp. 132- 136 ,(1992) , 10.1016/0003-9861(92)90498-L
K. Scharfenberg, R. Wagner, K.G. Wagner, The cytotoxic effect of ajoene, a natural product from garlic, investigated with different cell lines Cancer Letters. ,vol. 53, pp. 103- 108 ,(1990) , 10.1016/0304-3835(90)90201-8
Dennis V. Parke, Mechanisms of chemical toxicity—a unifying hypothesis Regulatory Toxicology and Pharmacology. ,vol. 2, pp. 267- 286 ,(1982) , 10.1016/0273-2300(82)90001-0
John J. Lemasters, James DiGuiseppi, Anna-Liisa Nieminen, Brian Herman, Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes Nature. ,vol. 325, pp. 78- 81 ,(1987) , 10.1038/325078A0
Stefania Miccadei, Marlene E. Kyle, Donna Gilfor, John L. Farber, Toxic consequence of the abrupt depletion of glutathione in cultured rat hepatocytes. Archives of Biochemistry and Biophysics. ,vol. 265, pp. 311- 320 ,(1988) , 10.1016/0003-9861(88)90133-6
Stefania Miccadei, Dai Nakae, Marlene E. Kyle, Donna Gilfor, John L. Farber, Oxidative cell injury in the killing of cultured hepatocytes by allyl alcohol Archives of Biochemistry and Biophysics. ,vol. 265, pp. 302- 310 ,(1988) , 10.1016/0003-9861(88)90132-4