Naphthoquinones from Onosma paniculata Induce Cell-Cycle Arrest and Apoptosis in Melanoma Cells

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• 作者：Nadine Kretschmer ; Beate Rinner ; Alexander J. A. Deutsch ; Birgit Lohberger ; Heike Knausz ; Olaf Kunert ; Martina Blunder ; Herbert Boechzelt ; Helmut Schaider ; Rudolf Bauer
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：May 25, 2012
• 年：2012
• 卷：75
• 期：5
• 页码：865-869
• 全文大小：248K
• 年卷期：v.75,no.5(May 25, 2012)
• ISSN：1520-6025

文摘

Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, 尾-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of 伪-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death.