Identification of a Wells-Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity
| Autor: | Qian Lu, Jiamiao Hu, Michelle Gek Liang Lim, Shanshan Liu, Xiaodi Su, Kin Yip Tam, X.M. Wang, Kamesh Narasimhan, Prasanna R. Kolatkar, Congling Chen, Shie Hong Chang, Si Kee Tan, Ralf Jauch, Guimei Cui, Siu Yee New, Edwin Cheung, Harapriya Chakravarty |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures Apoptosis Breast Neoplasms Biochemistry Small Molecule Libraries 03 medical and health sciences Transcription (biology) Gene silencing Humans Molecular Biology Gene Transcription factor Cell Proliferation Cell growth Chemistry Cell Biology Tungsten Compounds Molecular biology Small molecule Kinetics 030104 developmental biology Transcription Factor AP-2 Female sense organs |
| Zdroj: | The Biochemical journal. 475(11) |
| ISSN: | 1470-8728 |
| Popis: | AP-2 gamma (AP-2γ) is a transcription factor that plays pivotal roles in breast cancer biology. To search for small molecule inhibitors of AP-2γ, we performed a high-throughput fluorescence anisotropy screen and identified a polyoxometalate compound with Wells–Dawson structure K6[P2Mo18O62] (Dawson-POM) that blocks the DNA-binding activity of AP-2γ. We showed that this blocking activity is due to the direct binding of Dawson-POM to AP-2γ. We also provided evidence to show that Dawson-POM decreases AP-2γ-dependent transcription similar to silencing the gene. Finally, we demonstrated that Dawson-POM contains anti-proliferative and pro-apoptotic effects in breast cancer cells. In summary, we identified the first small molecule inhibitor of AP-2γ and showed Dawson-POM-mediated inhibition of AP-2γ as a potential avenue for cancer therapy. |
| Databáze: | OpenAIRE |
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