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

We have screened tropical plant extracts for substances that induce normal morphology in K-ras(ts)-NRK cells. As a result we isolated an anthraquinone 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 temperature, without changing the amount and localization of Ras. The effect of damnacanthal was reversible, and the compound had no effect on the morphology of RSV(ts)-NRK cells expressing the src oncogene. Thus, damnacanthal is a new inhibitor of ras function.