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, anti-tumor 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 ± 0–250 uM 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 ~ ≥5 uM ATM, p<0.01), capillary proliferation was inhibited ≥10 uM (p<0.05). Arterial endothelium were less sensitive to ATM, (50% inhibition ~ ≥ 20 uM, p<0.01). YPEN-1 were inhibited >50 uM ATM. Capillary viability was inhibited ≥20 μM 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. Received 13 February 2007; returned for revision 10 April 2007; returned for final revision 1 June 2007; accepted by A. Falus 13 July 2007