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学科主题: 临床医学
题名:
Non-caspase-mediated apoptosis contributes to the potent cytotoxicity of the enediyne antibiotic lidamycin toward human tumor cells
作者: Wang, Z1; He, QY1; Liang, YY1; Wang, DS1; Li, YY1; Li, DD1
关键词: lidamycin ; DNA cleavage ; apoptosis ; caspases ; hepatoma BEL-7402 cells ; breast carcinoma MCF-7 cells
刊名: BIOCHEMICAL PHARMACOLOGY
发表日期: 2003-06-01
DOI: 10.1016/S0006-2952(03)00117-5
卷: 65, 期:11, 页:1767-1775
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: DNA FRAGMENTATION ; NUCLEAR EVENTS ; C-1027 ; CLEAVAGE ; INDUCTION ; C1027 ; DIFFERENTIATION ; CHROMOPHORE ; EXPRESSION ; CANCER
英文摘要:

Enediyne antibiotics have been reported to be the most potent cytotoxic antitumor agents. The pathway by which these compounds cleave DNA and induce apoptosis of tumor cells may be different from the caspase-mediated pathways that initiate typical apoptosis. In this report, we studied the apoptosis induced by lidamycin (LDM), a member of the enediyne antibiotic family, and compared the characteristics of LDM-induced apoptosis with those of typical apoptosis induced by mitomycin C or etoposide. Chromatin condensation occurred very rapidly and appeared as speckles in human hepatoma BEL-7402 and breast carcinoma MCF-7 cells after treatment with I muM LDM. In addition, co-staining the cells with the mitochondria-specific dye Mitosensor(TM) and the DNA-specific dye Hoechst 33342 enabled the visualization of mitochondria in normal control and LDM-treated cells but not in mitomycin C-treated cells. Neither the caspase inhibitor VAD-fmk nor the caspase-3 inhibitor DEVD-fmk was able to inhibit the DNA ladder patterns caused by LDM in BEL-7042 or MCF-7 cells. Smaller fragments of histone HI cleaved by LDM were detected by SDS-PAGE, indicating that the site of LDM action is the internucleosomal structure. Although caspase-9, caspase-3/7, and caspase-6 activities were increased in BEL-7402 cells, and caspase-7 activity was increased in MCF-7 cells after treatment with I muM LDM, this occurred much later, indicating that chromatin condensation reached the maximal level rapidly while caspase activities still remained low. Taken together, these results demonstrate that LDM induced rapid DNA cleavage and chromatin condensation independently of caspase activities; this may contribute to its highly potent cytotoxicity toward tumor cells. (C) 2003 Elsevier Science Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000183429900002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50543
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
2.Peking Union Med Coll, Beijing 100050, Peoples R China
3.Peking Univ, Sch Oncol, Beijing Inst Canc Res, Beijing 100034, Peoples R China
4.Berlex Biosci, Richmond, CA 94804 USA

Recommended Citation:
Wang, Z,He, QY,Liang, YY,et al. Non-caspase-mediated apoptosis contributes to the potent cytotoxicity of the enediyne antibiotic lidamycin toward human tumor cells[J]. BIOCHEMICAL PHARMACOLOGY,2003,65(11):1767-1775.
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