title: Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia quinata.
abstract: PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC50 values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 μM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC50 values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 μM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents.
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. ntopjp77@gmail.com.
authors.forename: Jin-Pyo
authors.initials: JP
authors.lastname: An
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. htkquy@ctu.edu.vn.
authors.forename: Thi Kim Quy
authors.initials: TK
authors.lastname: Ha
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. jwkim@snu.ac.kr.
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Kim
authors.affiliation: Marine Bio Research Center, Department of Life Science, Chosun University, Gwangju 501-759, Korea. tocho@chosun.ac.kr.
authors.forename: Tae Oh
authors.initials: TO
authors.lastname: Cho
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. wkoh1@snu.ac.kr.
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Akebia quinata; breast cancer; protein tyrosine phosphatase 1B (PTP1B); terpenes