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.


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 ~ > or =5 uM ATM, p<0.01), capillary proliferation was inhibited > or =10 uM (p<0.05). Arterial endothelium were less sensitive to ATM, (50% inhibition ~ > or = 20 uM, p<0.01). YPEN-1 were inhibited >50 uM ATM. Capillary viability was inhibited > or =20 microM 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.
Carpenter
A
A
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3932, USA.
Rassam
A
A
Jennings
M H
MH
Robinson-Jackson
S
S
Alexander
J S
JS
Erkuran-Yilmaz
C
C
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008982:Molybdenum / Q000494:pharmacology*; D051381:Rats
D020533:Angiogenesis Inhibitors; D008982:Molybdenum; C020809:tetrathiomolybdate