INDUCTION OF NORMAL PHENOTYPES IN RAS-TRANSFORMED CELLS BY DAMNACANTHAL FROM MORINDA-CITRIFOLIA

We have screened tropical plant extracts for substances that induce no rmal morphology in K-ras(ts)-NRK cells. As a result we isolated an ant hraquinone compound, damnacanthal, from the chloroform extract of the root of Morinda citrifolia. Damnacanthal induced normal morphology and cytoskeletal structure in K-ras(ts)-NRK cells at the permissive tempe rature, without changing the amount and localization of Ras. The effec t of damnacanthal was reversible, and the compound had no effect on th e morphology of RSV(ts)-NRK cells expressing the src oncogene. Thus, d amnacanthal is a new inhibitor of ras function.