engleski

In vitro toxicity of bisperoxovanadium compounds tested on different cell lines

The insulinomimetic properties of vanadate and vanadyl derivatives have been widely investigated both in vitro and in vivo. Studies by Posner et al. (1994) showed that a peroxovanadium compounds are far more potent as insulin receptor kinase activators and phosphotyrosine phosphatase inhibitors than vanadate. Stability and potency of these compounds randers them attractive agents in diabetes mellitus but their possible toxic effects on cells could put in question their therapeutic use. We investigate the effect of bisperoxovanadium complexes (bpV[phen]), bpV[pic] and bpV[ox] on the survival of rat pheochromocytoma cell line, PC12, and the human ovarian cancer cell line, OVCAR-3. we also investigated the ability of a mitogenic agent, epidermal growth factor (EGF), a differentiating agent, nerve growth factor (NGF), and an immunosupressive agent, FK-506, to reduce the toxicity of bpV. OVCAR-3 cells were less sensitive towards the toxic effects of these complexes as compared to PC12 cells. All three complexes affected OVCAR-3 cell survival to a similar extent, but bpV(phen) ( more than 20 microM) was the most toxic for PC12 cells. Treatment with a mitotic agent, EGF at 50 ng/mL, in combination with bpV(phen) ( 1 microM) reduced the number of dead cells when compared to treatment with EGF alone, in PC12 cells subjected to serum withdrawal. NGF, at 100 ng/mL, alone and in combination with 0.1 microM bpV(phen) prevented death of serum-deprived, non-differentiated PC12 cells. FK-506 (1 microM) alone or in combination with 1 microM bpV(phen) for 1 hour significantly enhanced cell survival after serum withdrawal in non-differentiated PC12. In conclusion, we show that concentrations greater than 10 microM bpV(phen) are toxic for cells whereas low micromolar concentrations of bpV(phen) can enhance cell survival especially in combination with NGF and FK-506.

peroxovanadium compounds; apoptosis

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