Eupatilin inhibits proliferation of ras-transformed human breast epithelial (MCF-10A-ras) cells

Artemisia asiatica Nakai has been used frequently in traditional Asian medicine for the treatment of inflammation and cancer. Eupatilin (5,7-dihydroxy-3',4', 6-trimethoxy-flavone) was shown to be a pharmacologically active ingredient of A asiatica. In the present study, we found that expression of cyclin D1, a key protein that regulates G(1)/S progression, was decreased in MCF-10A-ras cells treated with eupatilin. Downregulation of cyclin D1 expression by eupatifin was accompanied by a reduced expression of c-Jun and the DNA binding activity of the transcription factor AP-1. The expression of p21(waf1/Cip1) was also decreased by eupatilin treatment in both protein and the mRNA levels. We concluded that the inhibitory effect of eupatilin on p21(waf1/Cip1) expression is likely to be associated with the downregulation of cyclin D1 expression and AP-1 activation, which play an important role in the cell cycle arrest of ras-transformed breast epithelial cells.