Potential therapeutic advantage of ribose-cysteine in the inhibition of astrocytoma cell proliferation
- 261 Downloads
It has been observed that astrocyte and astrocytoma cells differ in their response to d-ribose-l-cysteine (RibCys) in the culture medium. RibCys, a prodrug of l-cysteine, elevates the level of cysteine and glutathione in both astrocytoma and astrocyte cultures. It also affects the activity of two sulfurtransferases, 3-mercaptopyruvate sulfurtransferase and rhodanese, involved in the metabolism of sulfane sulfur-containing compounds and in consequence exerts an effect on the level of sulfane sulfur. Under conditions, in which the raised level of sulfane sulfur was accompanied by an elevated activity of 3-mercaptopyruvate sulfurtransferase, the proliferation of the human astrocytome U373 line was decreased. The experiments were simultaneously performed with murine astrocytes to compare the behavior of normal cells under similar conditions. In murine astrocytes, RibCys was capable of increasing cellular proliferation, and was accompanied by a diminished level of sulfane sulfur and unchanged activity of the two sulfurtransferases. Thus, RibCys might offer a therapeutic advantage in the inhibition of astrocytoma cell proliferation. Besides, in the absence of oxidative stress, measured as the ratio of GSH/GSSG, the obtained results confirm that the fall in the level of sulfane sulfur is associated with increasing proliferation of cells, whereas a rise in the level causes a decrease in the proliferation of U373 cells.
KeywordsAstrocytes Cysteine Glutathione 3-Mercaptopyruvate sulfurtransferase Ribose-cysteine Rhodanese Sulfane sulfur U373 cells
This work was supported by a grant from the Polish Committee for Scientific Research (KBN) K/ZDS/000450 and K/ZBW/000147.
- Ghibellia L, Fanellia C, Rotilioa G, Lafaviaa E, Coppolaa S, Colussia C, Civitarealea P, Ciriolob MR (1998) Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB J 12:479–486Google Scholar
- Guebela DV, Torresb NV (2004) Dynamics of sulfur amino acids in mammalian brain: assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model. Biochim Biophys Acta 1674:12–28Google Scholar
- Hwang C, Sinskey AJ (1991) The role of oxidation-reduction potential in monitoring growth of mammalian cultured cells. In: Spier RE, Griffiths JB, Meignier B (eds) Production of biologicals from animal cells in culture. Halley Court, Oxford, pp 548–657Google Scholar
- Iwata S, Hori T, Sato N, Ueda-Taniguchi Y, Yamabe T, Nakamura H, Masutani H, Yodoi J (1994) Thiol-mediated redox regulation of lymphocyte proliferation: possible involvement of adult T cell leukemia-derived factor and glutathione in transferring receptor expression. J Immunol 152:5633–5642PubMedGoogle Scholar
- Meister A (1989) Metabolism and function of glutathione. In: Dolphin D, Poulson R, Avramovic O (eds) Glutathione: chemical and biochemical and medical aspects. Wiley, New York, pp 367–474Google Scholar
- Stavrovskaya AA (2000) Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc) 65:95–106Google Scholar
- Wood JL (1987) Sulfane sulfur. In: Jakoby WB, Griffith OW (eds) Methods in enzymology, vol 143. Academic Press, San Diego, pp 25–29Google Scholar