A novel anticancer agent ARC antagonizes HIV-1 and HCV

被引:17
作者
Nekhai, S.
Bhat, U. G.
Ammosova, T.
Radhakrishnan, S. K.
Jerebtsova, M.
Niu, X.
Foster, A.
Layden, T. J.
Gartel, A. L.
机构
[1] Univ Illinois, Coll Med, Dept Med, Chicago, IL 60612 USA
[2] Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA
[3] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA
[4] Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC 20059 USA
[5] CRI Ctr, Childrens Natl Med Ctr, Washington, DC 20059 USA
[6] Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA
关键词
HIV; HCV; anticancer drug; nucleoside analog;
D O I
10.1038/sj.onc.1210158
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public health concerns worldwide. HCV is clearly associated with the occurrence of hepatocellular carcinoma, and recently HIV infection has also been linked to the development of a multitude of cancers. Previously, we identified a novel nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that exhibited proapoptotic and antiangiogenic properties in vitro. Here, we evaluated the effect of ARC on HIV-1 transcription and HCV replication. Using reporter assays, we found that ARC inhibited HIV-1 Tat-based transactivation in different cell systems. Also, using hepatoma cells that harbor subgenomic and full-length replicons of HCV, we found that ARC inhibited HCV replication. Together, our data indicate that ARC could be a promising candidate for the development of antiviral therapeutics against HIV and HCV.
引用
收藏
页码:3899 / 3903
页数:5
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