Bioassay for the identification of natural product-based activators of peroxisome proliferator-activated receptor-gamma (PPARgamma): the marine sponge metabolite psammaplin A activates PPARgamma and induces apoptosis in human breast tumor cells.
Bioassay for the identification of natural product-based activators of peroxisome proliferator-activated receptor-gamma (PPARgamma): the marine sponge metabolite psammaplin A activates PPARgamma and induces apoptosis in human breast tumor cells.
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发表时间：
2006
影响因子：
5.1
通讯作者：
Flor D. Mora;Deborah K. Jones;P. Desai;Akshay Patny;M. Avery;D. Feller;T. Smillie;Yu-Dong Zhou;D. Nagle
中科院分区：
文献类型：
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作者：
Flor D. Mora;Deborah K. Jones;P. Desai;Akshay Patny;M. Avery;D. Feller;T. Smillie;Yu-Dong Zhou;D. Nagle
过氧化物酶体增殖物激活受体（PPARs）是核激素受体（NHR）家族的成员，是配体激活的转录因子。PPARgamma的配体（激动剂）已显示在人乳腺肿瘤细胞中抑制生长、促进终末分化和诱导凋亡。开发了一种基于细胞的报告基因测定，以检查陆地和海洋生物提取物激活PPARgamma的能力。生物测定引导的分级分离和分离来自Pseudoceratina rhax的活性提取物产生了已知的组蛋白脱乙酰酶（HDAC）抑制剂psammaplin A（1）。化合物1在基于MCF-7细胞的报告基因测定中活化PPARgamma并在体外诱导人乳腺肿瘤细胞的凋亡。分子模拟研究表明，1可能与PPARgamma配体结合口袋内的结合位点相互作用。因此，除了已知的对HDAC介导的过程的影响外，激活PPARgamma调节的基因表达可能在1诱导细胞凋亡的能力中发挥作用。
Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor (NHR) family, are ligand-activated transcription factors. Ligands (agonists) of PPARgamma have been shown to inhibit growth, promote terminal differentiation, and induce apoptosis in human breast tumor cells. A cell-based reporter assay was developed to examine extracts of terrestrial and marine organisms for the ability to activate PPARgamma. Bioassay-guided fractionation and isolation of an active extract from Pseudoceratina rhax yielded the known histone deacetylase (HDAC) inhibitor psammaplin A (1). Compound 1 activates PPARgamma in a MCF-7 cell-based reporter assay and induces apoptosis in human breast tumor cells in vitro. Molecular modeling studies suggest that 1 may interact with binding sites within the PPARgamma ligand-binding pocket. Therefore, in addition to its known effects on HDAC-mediated processes, activation of PPARgamma-regulated gene expression may play a role in the ability of 1 to induce apoptosis.