Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides

	Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides
	Zhang, Nan 1,2; Bing, Tao 1; Liu, Xiangjun 1; Qi, Cui 1; Shen, Luyao 1,2; Wang, Linlin 1; Shangguan, Dihua 1
刊名	CHEMICAL SCIENCE
	2015
卷号	6 期号:7 页码:3831-3838
英文摘要	Guanine-rich oligonucleotides (GROs) have attracted considerable attention as anticancer agents, because they exhibit cancer-selective antiproliferative activity and can form G-quadruplex structures with higher nuclease resistance and cellular uptake. Recently, a GRO, AS1411 has reached phase II clinical trials for acute myeloid leukemia and renal cell carcinoma. The antiproliferative activity of GROs has been associated with various protein targets; however the real mechanisms of action remain unclear. In this study, we showed evidence that antiproliferative activity of GROs (including AS1411) is mainly contributed by the cytotoxicity of their guanine-based degradation products, such as monophosphate deoxyguanosine (dGMP), deoxyguanosine (dG) and guanine. The GROs with lower nuclease resistance exhibited higher antiproliferative activity. Among nucleotides, nucleosides and nucleobases, only guanine-based compounds showed highly concentration-dependent cytotoxicity. Our results suggest that it is necessary to reconsider the cancer-selective antiproliferative activity of GROs. Since guanine-based compounds are endogenous substances in living organisms, systematic studies of the cytotoxicity of these compounds will provide new information for the understanding of certain diseases and offer useful information for drug design.
收录类别	SCI
语种	英语
公开日期	2016-05-09
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/27967]
专题	化学研究所_活体分析化学实验室
作者单位	1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Inst Chem, Key Lab Analyt Chem Living Biosyst, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Nan,Bing, Tao,Liu, Xiangjun,et al. Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides[J]. CHEMICAL SCIENCE,2015,6(7):3831-3838.
APA	Zhang, Nan.,Bing, Tao.,Liu, Xiangjun.,Qi, Cui.,Shen, Luyao.,...&Shangguan, Dihua.(2015).Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides.CHEMICAL SCIENCE,6(7),3831-3838.
MLA	Zhang, Nan,et al."Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides".CHEMICAL SCIENCE 6.7(2015):3831-3838.