title: A novel anti-cancer agent, acetyltanshinone IIA, inhibits oestrogen receptor positive breast cancer cell growth by down-regulating the oestrogen receptor.
abstract: In this paper we show that acetyltanshinone IIA (ATA), a novel anti-cancer agent, preferentially inhibits cell growth of oestrogen receptor positive (ER+) breast cancer cells and that it is more potent than the commonly used anti-breast cancer agent, tamoxifen. The metabolic product of ATA, hydroquinone tanshinone IIA (HTA) binds to the ERα and causes its degradation mainly in the nucleus via an ubiquitin-mediated proteasome-dependent pathway. In addition, ATA also reduced the mRNA levels of the ERα encoding gene, ESR1, distinguishing ATA from another anti-breast cancer drug, fulvestrant. Finally, ATA reduced the transcription of an ER-responsive gene, GREB1.
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Medical Oncology, Johns Hopkins Singapore International Medical Centre, Singapore.
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Lima Lopes
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore. Electronic address: kluo@ntu.edu.sg.
authors.forename: Kathy Qian
authors.initials: KQ
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002853:Chromatography, Liquid; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D010616:Phenanthrenes / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D010616:Phenanthrenes; D011960:Receptors, Estrogen; C552419:acetyltanshinone IIA
keywords: Acetyltanshinone IIA; Anti-breast cancer agent; Fulvestrant; Oestrogen receptor; Tamoxifen