title: Eupatilin inhibits proliferation of ras-transformed human breast epithelial (MCF-10A-ras) cells.
abstract: 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 G1/S progression, was decreased in MCF-10A-ras cells treated with eupatilin. Downregulation of cyclin D1 expression by eupatilin was accompanied by a reduced expression of c-Jun and the DNA binding activity of the transcription factor AP-l. The expression of p21waf1/Cip1 was also decreased by eupatilin treatment in both protein and the mRNA levels. We concluded that the inhibitory effect of eupatilin on p21waf1/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.
authors.affiliation: National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Na
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Oh
authors.forename: Chang-Yell
authors.initials: CY
authors.lastname: Shin
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D042361:Mammary Glands, Human / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018808:Transcription Factor AP-1; D019938:Cyclin D1; C045325:eupatilin; D004247:DNA; D051358:Cyclin-Dependent Kinase 4