title: Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.
abstract: Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. yoojin0909@hanmail.net.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea. cuijun928@naver.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
authors.affiliation: KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. junlee@kiom.re.kr.|Korean Medicine Life Science, University of Science &amp; Technology, Daejeon 34054, Korea. junlee@kiom.re.kr.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. andyhanandy@naver.com.
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Han
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea. jojnstar@naver.com.
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea. hhjang@gachon.ac.kr.|Gachon Medical Research Institute, Gil Hospital, Incheon 405-760, Korea. hhjang@gachon.ac.kr.
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. yuny@ewha.ac.kr.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Seo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D031324:Juglans / Q000737:chemistry*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: 5-hydroxy-2-methoxy-1,4-naphthoquinone; 8-hydroxy-2-methoxy-1,4-naphthoquinone; Juglandaceae; Juglans sinensis Dode; antiproliferative activity; apoptosis; cytotoxicity