[Molecular genetic aspects of the antineoplastic effect of gluthoxim]

Gluthoxim--bis(g-L-gluthamyl)-L-cystenyl-bis-glycin disodium salt (C20H32O16N6S2)--is an analog of oxidized gluthation with a stable disulfide bond. It is a drug of a new class of thiopoetins which regulate thiol disulfide metabolism. Gluthoxim is used as a support substance in chemotherapy of cancer. The present investigation deals with feasibility of gluthoxim-induced apoptosis in tumor cell cultures, including human myeloleukema cells HL60 which lack protein p53 gene, so crucial for apoptosis. Also, gluthoxim effect was studied with respect to transformed murine fibroblasts C8 and A4, carrying the plasmide structure with Ras and E1A genes which boost Ras-gene expression. This in turn makes fibroblasts ready to start apoptosis. Gluthoxim induction of cell death was demonstrated in both cell lines; however, apoptosis in cells C8 (with intact gene p53) was much more pronounced than in cells A4 without this gene. It is suggested that apoptosis can be triggered by both imbalance of redox potential typical of tumor cells, induction of p53 synthesis and an impact on the phosphoproteinase cascade of Ras-signal pathway.