Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC 50 value of 13.8 μM, which was less potent than copper(II) chloride (IC 50 5.3 μM). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells.

Gastric emptying was studied in CD-1 mice weighing 15-30 g. Mice were fed a nonabsorbable test meal consisting of radioactive barium sulfate suspended in 1.5% methylcellulose. The amount of test meal remaining in the stomach was determined 1, 2, 5, and 10 min after the administration. The initial rates of emptying were significantly higher in the groups weighing 15-20 g body wt. In all groups, 50% of the radioactivity administered was emptied in less than 5 min. The gastric emptying figures obtained were adjusted to three general equations: exponential, hyperbolic, and parabolic. The best correlation coefficients were obtained with the parabola, although this pattern of emptying is not completely satisfactory because it has a minimum before the 10th min. The comparison of the exponential and hyperbolic patterns, in terms of both the correlation coefficients and the "starting indexes," showed that the hyperbola describes the data more closely. No sex differences were observed.

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