Document Detail

Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species.
MedLine Citation:
PMID:  19758808     Owner:  NLM     Status:  MEDLINE    
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 microM) and 23 (20 and 50 microM) for 24h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 microM) and 23 (20 and 50 microM) 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.
Huang-Yao Tu; A-Mei Huang; Bai-Luh Wei; Kim-Hong Gan; Tzyh-Chyuan Hour; Shyh-Chyun Yang; Yeong-Shiau Pu; Chun-Nan Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-27
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  17     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-06     Completed Date:  2010-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  7265-74     Citation Subset:  IM    
Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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MeSH Terms
Apoptosis / drug effects*
Cell Cycle / drug effects*
Cell Line, Tumor
Magnetic Resonance Spectroscopy
Reactive Oxygen Species / metabolism*
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Infrared
Triterpenes / chemistry,  pharmacology*
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Triterpenes; 77-52-1/ursolic acid

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