REVERSION OF V-H-RAS-TRASFORMED NIH 3T3 CELLS BY APIGENIN THROUGH INHIBITING MITOGEN-ACTIVATED PROTEIN-KINASE AND ITS DOWNSTREAM ONCOGENES

Apigenin, a plant flavonoid, induced the reversion of transformed phenotypes of v-H-ras-transformed NIH 3T3 cells at a quite low concentration of 12.5 mu M. In the present study, we have examined the components of this Ras-mediated signaling transduction to determine whether they were involved in the apigenin-induced reversion process. Interestingly, the consitutively activated mitogen activated protein kinase (MAPK) in the ras transformant was inhibited significantly and rapidly by 25 mu M apigenin within 30 min, and this reduction continued for more than 4 h. Corroborating these observations, expression of the downstream oncogenes c-jun and c-fos was also dramatically reduced during the first 4 h of treatment. We found that the levels of ras protein and mRNA were not affected by 24 h of treatment with apigenin. These findings indicate that apigenin-induced reversion of v-H-ras-transformed NIH 3T3 cells may occur by inhibiting MAPK activity and its downstream oncogenes rather than by affecting the expression of the ras gene. (C) 1995 Academic Press, Inc.