title: Germacrone Inhibits Estrogen Receptor α-Mediated Transcription in MCF-7 Breast Cancer Cells.
abstract: Estrogen receptor (ER)α-positive breast cancer cells regulate the expression of estrogen-responsive genes, which are involved in cell proliferation, differentiation, and cell cycle progression. Clinically, the inhibition of ERα-mediated gene expression in breast cancer cells has long been considered an effective way to prevent the development and progression of cancer. Germacrone, a terpenoid compound isolated from Rhizoma curcuma, has been known to have antitumor activity in various human cancer cell lines. However, the mechanism by which germacrone inhibits the proliferation of breast cancer cells is still unclear. Here, we demonstrated that germacrone inhibits ERα-mediated gene expression at the transcriptional level in MCF-7 cells. Germacrone inhibits the recruitment of ERα to the estrogen response element on chromatin and consequently compromises the binding of switch/sucrose non-fermentable chromatin remodeling complex and RNA polymerase II to target gene promoter, thereby inhibiting the estrogen-induced chromatin accessibility. In addition, germacrone efficiently potentiates the antitumor activity of methotrexate and 5-fluorouracil. Our results not only provide substantial molecular mechanism of germacrone on ERα-mediated signaling in breast cancer cells but also demonstrate the benefits of germacrone as a combination therapy with other drugs for the treatment of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, Korea.
authors: Mi-Sun
authors: MS
authors: Lim
authors: Department of Preventive Pharmacy and Toxicology, Department of Life and Nanopharmaceutical Science of Pharmacy, College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Korea.
authors: Se-Young
authors: SY
authors: Choung
authors: Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, Korea.
authors: Kwang Won
authors: KW
authors: Jeong
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha; D045788:Sesquiterpenes, Germacrane; C048393:germacrone
keywords: breast cancer; estrogen receptor; germacrone; transcription