JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.
JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.
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DOI：
10.1211/jpp.62.01.0017
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Shami PJ
中科院分区：
文献类型：
--
作者：
Kiziltepe T;Anderson KC;Kutok JL;Jia L;Boucher KM;Saavedra JE;Keefer LK;Shami PJ
Glutathione S-Transferases (GST) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases NO on metabolism by GST. O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-neoplastic activity. We studied the effect of JS-K on angiogenesis. JS-K inhibited the proliferation of HUVEC’s with a 50% inhibitory concentration (IC50) of 0.432, 0.466, and 0.505 µM at 24, 48, and 72 hours, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 µM, respectively. JS-K inhibited cell migration at 5 hours using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 µM. In the chick aortic ring assay using VEGF or FGF-b for vessel growth stimulation, 0.5 µM JS-K completely inhibited vessel growth. JS-K inhibited tumor angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. JS-K is a potent inhibitor of angiogenesis in vitro and tumor vessel growth in vivo. As such, it establishes a new class of anti-neoplastic agents that target the malignant cells directly as well as their microenvironment.
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