Preferential targeting cancer-related i-motif DNAs by the plant flavonol fisetin for theranostics applications
Preferential targeting cancer-related i-motif DNAs by the plant flavonol fisetin for theranostics applications
复制标题
植物黄酮醇非瑟酮优先靶向癌症相关 i-motif DNA，用于治疗诊断学应用
DOI：
10.1038/s41598-020-59343-2
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发表时间：
2020
影响因子：
4.6
通讯作者：
Bhowmik Sudipta
中科院分区：
文献类型：
--
作者：
Takahashi Shuntaro;Bhattacharjee Snehasish;Ghosh Saptarshi;Sugimoto Naoki;Bhowmik Sudipta
i-motif DNA与癌症的关系促进了特异性配体的发展，以检测和调节它们的形成。一些植物黄酮醇显示出独特的荧光和抗癌特性，这表明与i基序DNA相关的癌症治疗的治疗诊断学方法的实用性。我们研究了植物黄酮醇非瑟酮（Fis）对i-motif DNA理化性质的影响。Fis与人血管内皮生长因子（VEGF）基因启动子区的i基序结合显著诱导了激发态分子内质子转移（ESIPT）反应，该反应显著增强了Fis的互变异构体发射带的强度。这种独特的反应是由于从i-基序到发夹样结构的结构变化的一致性，发夹样结构通过i-基序的环区域内的一些鸟嘌呤和结构中的胞嘧啶之间的假定的沃森-克里克碱基对来稳定。结果，VEGF i基序在Fis存在下不作为复制阻断物，这表明Fis用于调节VEGF基因表达的适用性。Fis的荧光和生物学特性可用于与特定癌症相关基因（例如VEGF）相关的癌症的治疗诊断学应用。
The relationship of i-motif DNAs with cancer has prompted the development of specific ligands to detect and regulate their formation. Some plant flavonols show unique fluorescence and anti-cancer properties, which suggest the utility of the theranostics approach to cancer therapy related to i-motif DNA. We investigated the effect of the plant flavonol, fisetin (Fis), on the physicochemical property of i-motif DNAs. Binding of Fis to the i-motif from the promoter region of the human vascular endothelial growth factor (VEGF) gene dramatically induced the excited state intramolecular proton transfer (ESIPT) reaction that significantly enhanced the intensity of the tautomer emission band of Fis. This unique response was due to the coincidence of the structural change from i-motif to the hairpin-like structure which is stabilized via putative Watson-Crick base pairs between some guanines within the loop region of the i-motif and cytosines in the structure. As a result, the VEGF i-motif did not act as a replication block in the presence of Fis, which indicates the applicability of Fis for the regulation of gene expression of VEGF. The fluorescence and biological properties of Fis may be utilised for theranostics applications for cancers related to a specific cancer-related gene, such as VEGF.