Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells

doi:10.1016/S0014-5793(01)02633-3

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	Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells
	Meng, LH; Ding, J
刊名	FEBS LETTERS
	2001-07-13
卷号	501 期号:1 页码:59-64
关键词	salvicine P2 promoter DNA damage c-myc DNA topoisomerase II inhibitor
ISSN号	0014-5793
DOI	10.1016/S0014-5793(01)02633-3
文献子类	Article
英文摘要	Salvicine is a novel diterpenoid quinone derivative possessing strong antitumor activities and was demonstrated to stabilize the DNA topoisomerase II (Topo II) cleavage complex in vitro and in vivo. In the present work we investigated the possible mechanism through which disturbance of Topo II by salvicine led to cell death. We found that salvicine induced DNA strand breaks in human promyelocytic leukemia HL-60 cells and DNA damage correlated with cell growth inhibition. DNA damage induced by brief exposure to salvicine could be partially reversed, but early DNA breaks triggered the process of apoptosis, Preferential damage in the P2 promoter region of the oncogene c-myc was detected, whereas no obvious DNA damage was found in the 3 ' region of the same gene, Furthermore, the expression of some protooncogenes such as c-myc, c-fos and c-jun was examined, showing that salvicine produced a reduction in the transcription rate of c-myc in a dose-dependent manner and a marked induction of c-fos and c-jun expression was observed. It appears possible that DNA damage within such genomic regions is an early event, which could lead to growth inhibition mediated by alterations of the expression of selected proliferation regulatory genes, such as c-myc, c-fos and c-jun, and ultimately cell death. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
WOS关键词	DIFFERENTIAL INDUCTION ; GENE-EXPRESSION ; LEUKEMIA-CELLS ; CYTO-TOXICITY ; PROTOONCOGENE ; EPIPODOPHYLLOTOXINS ; INHIBITORS ; AMSACRINE ; CLEAVAGE ; CANCER
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000169947800011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274470]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, J
作者单位	Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Div Antitumor Pharmacol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Meng, LH,Ding, J. Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells[J]. FEBS LETTERS,2001,501(1):59-64.
APA	Meng, LH,&Ding, J.(2001).Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells.FEBS LETTERS,501(1),59-64.
MLA	Meng, LH,et al."Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells".FEBS LETTERS 501.1(2001):59-64.