Two potentially angiostatic factors, a steroid and L-azetidine-2-carboxylic acid, antagonize one another

The proline analogue L-azetidine-2-carboxylic acid (LACA) systemically suppressed mast-cell-mediated angiogenesis, as measured by the rat mesenteric-window method. Dexamethasone and methylprednisolone at very low and non-toxic s.c. doses also somewhat inhibited the angiogenesis. Most interestingly, the co-administration of either of these steroids with LACA paradoxically stimulated angiogenesis. These findings suggest that in the future search for candidates for clinically-useful systemic angiostatic remedies, one may have to focus not only on the effect of individual drugs or agents, but also on the effect of such putative anti-angiogenic agents when co-administered. The fact that two potentially angiostatic agents can antagonize one another has not previously been reported.