https://scholars.lib.ntu.edu.tw/handle/123456789/544451
標題: | Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species | 作者: | Tu H.-Y. Huang A.-M. Wei B.-L. Gan K.-H. Hour T.-C. Yang S.-C. YEONG-SHIAU PU Lin C.-N. |
關鍵字: | Anticancer; Cell cycle; Cytotoxicity; NTUB1; ROS; SAR; Seco-compound; Synthesis; Ursolic acid derivatives | 公開日期: | 2009 | 卷: | 17 | 期: | 20 | 起(迄)頁: | 7265-7274 | 來源出版物: | Bioorganic and Medicinal Chemistry | 摘要: | Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 μM) and 23 (20 and 50 μM) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 μM) and 23 (20 and 50 μM) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h. ? 2009 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-71749115319&doi=10.1016%2fj.bmc.2009.08.046&partnerID=40&md5=0c894e241870c8a8c951308b555aa5e1 https://scholars.lib.ntu.edu.tw/handle/123456789/544451 |
ISSN: | 0968-0896 | DOI: | 10.1016/j.bmc.2009.08.046 | SDG/關鍵字: | isopropyl 3beta hydroxyurs 12 en 28 oate; reactive oxygen metabolite; unclassified drug; ursolic acid; ursolic acid derivative; apoptosis; article; cell cycle arrest; cell cycle G1 phase; cell cycle G2 phase; cell cycle M phase; controlled study; drug cytotoxicity; flow cytometry; human; human cell; microtubule assembly; Apoptosis; Cell Cycle; Cell Line, Tumor; Humans; Magnetic Resonance Spectroscopy; Reactive Oxygen Species; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Triterpenes |
顯示於: | 醫學系 |
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