Identification of a Wells-Dawson polyoxometalate-based AP-2{gamma} inhibitor with pro-apoptotic activity

AP-2 gamma (AP-2) is a transcription factor that plays pivotal roles in breast cancer biology. To search for small molecule inhibitors of AP-2, 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-2. We showed that this blocking activity is due to the direct binding of Dawson-POM to AP-2. We also provided evidence to show that Dawson-POM decreases AP-2-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-2 and showed Dawson-POM-mediated inhibition of AP-2 as a potential avenue for cancer therapy.

Source: Biochemical Journal - June 11, 2018 Category: Biochemistry Authors: Hu, J., Tan, S. K., Lim, M. G. L., Chang, S. H., Cui, G., Liu, S., Narasimhan, K., New, S. Y., Wang, X., Chen, C., Chakravarty, H., Kolatkar, P. R., Tam, K. Y., Lu, Q., Su, X., Jauch, R., Cheung, E. Tags: Research Articles Source Type: research