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    Pyrrole-imidazole polyamide (PIP) can specifically bind in the B-DNA minor groove that has been used in several biological applications, such as anti-cancer activity, gene expression and translation control, and visualization of complex genomic areas. c-kit is a family member of the Tyrosine Kinase (RTK) type III receptor and plays a vital role in tumor growth, proliferation, differentiation, and cell apoptosis; however, its mutations and overexpression induce tumor dysfunction. Here, we designed and synthesized five matched PIPs that can recognize and bind to the DNA sequence in the oncogene c-kit promoter region, and evaluated their anti-cancer activity. The RTCA assay findings revealed that the PIPs would prevent the proliferation of cancer cells A549 and SGC-7901. EMSA assay showed that the PIPs were actively interacting with the c-kit gene target DNA. RT-PCR and Western blot assays have an effect on expression levels of the c-kit gene in the presence of PIPs. Flow cytometry and wound-healing assays showed that PIPs 4, 5 would cause apoptosis of cancer cells and inhibit the migration of cells, respectively. Overall findings indicate that PIP 5 has a relatively significant intracellular and extracellular impact on the target, contributing to migration and proliferation reduction, and cancer cell apoptosis. In addition, PIP has a certain ability to evolve into c-kit gene-targeting drugs. Copyright © 2020 Elsevier Masson SAS. All rights reserved.


    Mi Zhang, Jing Liang, Shi-Kun Jiang, Ling Xu, Yan-Ling Wu, Annoor Awadasseid, Xiao-Yin Zhao, Xu-Qiong Xiong, Hiroshi Sugiyama, Wen Zhang. Design, synthesis and anti-cancer activity of pyrrole-imidazole polyamides through target-downregulation of c-kit gene expression. European journal of medicinal chemistry. 2020 Dec 01;207:112704

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    PMID: 32866755

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