Within the concentration range of 1-20 FM, orthovanadate (Na ! VO ") demonstrated a time and dose-dependent inhibition of autocrine growth of the human carcinoma cell lines A549 (lung), HTB44 (kidney) and DU145 (prostate), as compared to appropriate controls (without Na ! VO "). The investigation was conducted by two methods: staining with N-hexa-methylpararosaniline (crystal violet=CV) or bromide3-(4,5-dimethyltio-azo-2)-2,5-diphenyl-tetrazole (MTT). In 5, 10 and 20 FM of Na ! VO " in serum-free medium, the mean values of these two tests for A549 were approximately 40%, 45% or 65% as compared to the appropriate controls. HTB44 had the greatest opportunity (statistically insignificant) at lower vanadium concentrations (up to 10 FM), whereas at 20 FM growth inhibition of these cells was approximately 50% of the controls. DU145 showed approximately 33%, 65% and 98% growth inhibition for 5, 10 and 20 FM of Na ! VO " , respectively Additionally, hypothetical curves obtained by a MANOVA test based on the CV results after 72 h incubation with Na ! VO " in serum-free medium, and an example of a time-dependent effect of Na ! VO " on A549 cells, were also presented. Sodium orthovanadate was also examined for its cytotoxic capabilities, especially its ability to induce tumor cell apoptosis; the results were compared with the effect of paclitaxel. The target cells were dyed by differential staining (HOECHST33258 and propidium iodide) after 3 h and 24 h (DU145) or 3 h and 72 h (A549) of incubation with the vanadium compound. Contrary to the two cancer cell lines (viable, apoptotic or necrotic in experimental conditions), the renal HTB44 cells were insensitive up to 15 FM Na ! VO " concentrations. After 3 h incubation with Na ! VO " , both lung (A549) and prostate (DU145) cancer cells showed a slight but significant reduction in the percentage of viable cells, and an increased amount of apoptotic cells. In contrast to the lung cells, DU145 prostate cells after 24 h were more sensitive to paclitaxel than to sodium orthovanadate. In the case of lung cells, the time of incubation was prolonged (to 72 h) to allow for a study of the effect of orthovanadate in greater detail. After 72 h of incubation with Na ! VO " or paclitaxel, A549 showed a similar level of viable cells (25-32% of total cultured cells); however, the percentage of apoptotic cells was higher in the case of A549 cells ca 36% for both drugs, but the concentration of Na ! VO " was significantly greater than paclitaxel levels.

Recent studies have shown the insulin-like effect of vanadyl sulphate or sodium ortho (or meta-)vanadate administered orally to rats. Toxicity of these drugs and reluctance by the animals to drink the solutions and take food, concerning the amelioration of some diabetes syndrome discussed in 1994 by Domingo et al. (1), McNeill et al. (2) and Wiliams and Malabu (3), prompted us to investigate a new vanadate complex: disodium bis(oxalato)oxovanadate (IV), Na2[VO(OX)2]H2O. The main object of the experiment was to study whether this complex administered as 3 mmol/l solution in 0.5% NaCl during 7 days could act on the subcellular level and influence the activity of liver Golgi membrane galactosyltransferase activity. Free blood sugar level was lowered (but was still higher than in the control group) in diabetic rats after seven days of vanadate action and was accompanied by lowered, however not statistically significant, serum triglyceride levels. The yields of isolated Golgi-rich membrane fractions were about half of the level in diabetic groups (untreated and treated with vanadium) compared with the control groups. Purity of these membrane fractions, expressed as nmol Gal transferred per mg of proteins and per h, was the same in four groups investigated and showed the possibility to compare them. Activity of galactosyltransferase calculated in nmol Gal transferred per 1 g of liver and per 1 h or per whole liver in the same time (as a possibility of glycosylation of the secretory and membrane glycoproteins) was lower in both diabetic groups. However, after vanadium treatment (D+V group), the activity was higher than in untreated diabetic rats (D group) in three of five investigated animals. Vanadyl-oxalate complex did not normalize in a statistically significant manner the enzyme activity which was significantly lower in diabetes than in control. This is similar to insulin influence on the galactosyltransferase activity reported previously by Kaczmarski et al. in 1981 (4) and Kordowiak et al. in 1981 (5).

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In vitro addition of 16,16'-dimethyl prostaglandin E2 to Golgi-rich membrane fraction in final concentration of 0.1 microgram/1 mg of protein increased generally the activity of galactosyltransferase in comparison with control. The percentage of phospholipids in the whole fraction was similar in both investigated groups, only the sum of phosphatidylethanolamine+phosphatidic acid was significantly lower after addition of dmPGE2 than in the control (0.001 < P < 0.01).