EFFECT OF DEHYDRODIDEMNIN-B ON HUMAN COLON-CARCINOMA CELL-LINES

Didemnins are cytotoxic agents belonging to a depsipeptide family isol ated from marine tunicates. In the present study, a new member, dehydr odidemnin B (DDB), isolated from the mediterranean tunicate Aplidium a lbicans, was used. The effect of the drugs on human colon cultured cel l lines was tested using multiple approaches: proliferation studies, l ong term survival after three hours of exposure to DDB by means of a c lonogenic assay and the decrease of the protooncogen, ornithine decarb oxylase, activity. A dehydrodidemnin B concentration of 10(-8) M compl etely inhibited cell growth. The IC50 obtained using the MTT prolifera tion test, indicated that the most proliferative cell line (CT-2) was the most sensitive to the drug. Using a clonogenic assay a clear dose- response was obtained for the three cell lines used; HT-29 cell line s howed the minimum survival after 3 hours of dehydrodidemnin B treatmen t. A dose-dependent decrease in ornithine decarboxylase activity was a lso observed in three cell lines assayed. The data presented indicate that the dehydrodidemnin B is a potent cytotoxic agent on rapidly divi ding human colon cancer cells.