期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 184, 期 3, 页码 439-448出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.01.041
关键词
Naphthoquinones; Juglone; Cytotoxicity; Apoptosis; Caspases; Cell cycle
资金
- CNPq
- CSIC-CNPq
- DGICYT Spain [BQU2003-00813, SAF2006-04698]
- CAPES
- FUNCAP
- FINEP
- BNB/FUNDECI
- FAPEAL
- MCT/DECIT
- MCT/MS/Neoplasias
- IM-INOFAR/CNPq
- PRONEX/FAPEAL
The cytotoxicity of nine naphthoquinones (NQ) was assayed against HL-60 (leukaemia), MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human cancer cell lines, and peripheral blood mononuclear cells (PBMC), as representatives of normal cells, after 72 h of incubation. 5-Methoxy-1,4-naphthoquinone was the most active compound, showing IC(50) values in the range of 0.31 (1.7 mu M) in HL-60 to 0.88 mu g/mL (4.7 mu M) in SF-295 and IC(50) of 0.69 mu g/mL (3.7 mu M) against PBMC. With the introduction of a bromo-substituent in position 2 or 3 of juglone, the IC(50) significantly decreased, regardless of the position on the NQ moiety. However, compared with juglone methyl ether, the halogen substitution decreased the activity. To further understand the mechanism underlying the cytotoxicity of 5-methoxy-1,4-naphthoquinone, studies involving DNA fragmentation, cell cycle analysis, phosphatidyl serine externalization, mitochondrial depolarization and activation of caspases 8 and 3/7 were performed in HL-60 cell line, using doxorubicin as a positive control. The results indicate that the cytotoxic 5-methoxy-1,4-naphthoquinone activates caspases 8 and 3/7 and thus induces apoptosis independent of mitochondria. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据