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Journal of Environmental Pathology, Toxicology and Oncology

Impact factor: 1.107

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v24.i4.20
pages 251-260

Eupatilin Inhibits Proliferation of ras-Transformed Human Breast Epithelial (MCF-10A-ras) Cells

Do-Hee Kim
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea
Hye-Kyung Na
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea
Tae Young Oh
Dong-A Pharmaceutical Co. Ltd., Kyunggido, South Korea
Chang-Yell Shin
Dong-A Pharmaceutical Co. Ltd., Kyunggido, South Korea
Young-Joon Surh
Seoul National University, South Korea

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.