Effects of ammonium tetrathiomolybdate, an oncolytic/angiolytic drug on the viability and proliferation of endothelial and tumor cells

Objective: This study examines the target specificity of tetrathiomolybdate (ATM), an anti-angiogenic, antitumor agent against the viability / proliferation of arterial, venous, capillary endothelial and tumor cells. Materials and Methods: Cells were seeded at 10 or 100% density (to measure viability / proliferation respectively) in medium +/- 0-250uM ATM. Viability and proliferation were measured by metabolic labeling-colorimetry. One-way ANOVA + Bonferroni testing examined base metabolism; Dunnett's testing was used for viability/proliferation. Results: Venous proliferation showed high ATM sensitivity (50% reduction similar to >= 5uM ATM, p<0.01), capillary proliferation was inhibited >= 10uM (p<0.05). Arterial endothelium were less sensitive to ATM, (50% inhibition similar to >= 20uM, p<0.01). YPEN-1 were inhibited >50uM ATM. Capillary viability was inhibited >= 20 mu M ATM (p<0.01); venous, arterial and tumor viability show less ATM sensitivity. Conclusions: Our data suggest that venous and capillary endothelial proliferation are important targets in ATM therapy, but that other vascular segments and tumor cells may be less influenced.