Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication.
Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication.
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DOI：
10.1186/1471-2407-4-70
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发表时间：
2004-09-30
期刊：
影响因子：
3.8
通讯作者：
Jung JH
中科院分区：
文献类型：
--
作者：
Jiang Y;Ahn EY;Ryu SH;Kim DK;Park JS;Yoon HJ;You S;Lee BJ;Lee DS;Jung JH
SV 40 DNA复制系统是理解复制机制的一个非常有用的工具，复制是一个严格调控的过程。许多环境和细胞因素可以通过抑制DNA复制来诱导细胞周期停滞或凋亡。在我们从海绵中寻找生物活性代谢产物的过程中，发现psammaplin A具有一定的抗癌活性，并对其可能的作用机制进行了研究。通过细胞计数试剂盒-8（CCK-8）测定细胞活力，以通过合并2-（2-甲氧基-4-硝基苯基）-3-（4-硝基苯基）-5-（2，4-二磺基苯基）-2H-四唑（WST-8）和1-甲氧基-吩嗪硫酸甲酯（1-甲氧基-PMS）计数活的RAW264.7细胞。在体外SV 40 DNA复制系统中研究了psammaplin A对DNA复制的影响。用超螺旋质粒DNA松弛法和[3 H]dTTP掺入法分别测定拓扑异构酶I和聚合酶α引发酶的活性。采用凝胶迁移率改变试验（GMSA）测定RPA的ssDNA结合活性。我们已经发现psammaplin A对RAW 264.7细胞系具有显著的细胞毒活性。同时发现psammaplin A在体外能显著抑制SV 40 DNA的复制，其中聚合酶α-引发酶是其主要作用靶点之一。综上所述，我们认为psammaplin A诱导的细胞毒性可能与其对DNA复制的抑制有关。Psammaplin A具有开发为抗癌药物的潜力。
SV40 DNA replication system is a very useful tool to understand the mechanism of replication, which is a tightly regulated process. Many environmental and cellular factors can induce cell cycle arrest or apoptosis by inhibiting DNA replication. In the course of our search for bioactive metabolites from the marine sponges, psammaplin A was found to have some anticancer properties, the possible mechanism of which was studied. Cell viability was determined by Cell Counting Kit-8 (CCK-8) to count living RAW264.7 cells by combining 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8) and 1-methoxy-phenazine methosulfate (1-methoxy-PMS). The effect of psammaplin A on DNA replication was carried out in SV40 DNA replication system in vitro. The activities of topoisomerase I and polymerase α-primase were measured by the relaxation of superhelical plasmid DNA and the incorporation of [3H]dTTP to the template respectively. The ssDNA binding activity of RPA was assessed by Gel Mobility Shift Assay (GMSA). We have found that psammaplin A delivers significant cytotoxic activity against the RAW264.7 cell line. It was also found that psammaplin A could substantially inhibit SV40 DNA replication in vitro, in which polymerase α-primase is one of its main targets. Taken together, we suggest that psammaplin A-induced cytotoxicity may correlate with its inhibition on DNA replication. Psammaplin A has the potential to be developed as an anticancer drug.
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DOI：
10.1073/pnas.090084797
发表时间：
2000-05-09
影响因子：
11.1
作者：
Morita, Y;Naka, T;Kishimoto, T
通讯作者：
Kishimoto, T
影响因子：
4.8
作者：
LEE, SH;KIM, DK
通讯作者：
KIM, DK
影响因子：
6.7
作者：
Kim, DY;Lee, IS;Yang, SI
通讯作者：
Yang, SI
影响因子：
3.5
作者：
Tabudravu, JN;Eijsink, VGH;van Aalten, DMF
通讯作者：
van Aalten, DMF
影响因子：
5.3
作者：
COLLINS, KL;KELLY, TJ
通讯作者：
KELLY, TJ