Anti-angiogenic and apoptotic effects of metabolites of sulindac on chick embryo chorioallantoic membrane.
Sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs), in addition to anti-inflammatory properties, express preventive activity against colon cancer. This antineoplastic effect may result from the suppression of polyp development in patients with familial adenomatous polyposis. However, despite intense investigations the exact mechanism for sulindac protective effect is not fully elucidated. Angiogenesis, the process of new blood vessel formation, is required to support tumor growth and may be partially involved in the transformation of polyps into tumor. Therefore, we tested the hypothesis whether sulindac might inhibit angiogenesis. The effects of sulindac metabolites, sulindac sulfide and sulindac sulfone, on vascular development were evaluated using the chick embryo chorioallantoic membrane (CAM) assay in vivo. The angiogenic response was quantitated by several methods including direct stereomicroscopic observation, measurements of hemoglobin content and DNA synthesis whereas quantitation of apoptosis was based on determinations of caspase-3 activity, caspase-3 and bax protein expression, and nuclear DNA fragmentation. Our results indicated that both sulindac metabolites were equally effective in inhibition of new blood vessel formation in CAM during chick embryo development. Moreover, both metabolites of sulindac induced the process of apoptosis parallelly to the inhibition of angiogenesis.