Identification of a Wells-Dawson polyoxometalate-based AP-2 γ inhibitor with pro-apoptotic activity.

Identification of a Wells-Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity. Biochem J. 2018 May 14;: Authors: Hu J, Tan SK, Lim MGL, Chang SH, Cui G, Liu S, Narasimhan K, New SY, Wang X, Chen C, Chakravarty H, Kolatkar PR, Tam KY, Lu Q, Su X, Jauch R, Cheung E Abstract 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 this blocking activity is due to the direct binding of Dawson-POM to AP-2γ. We also provide 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 have 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. PMID: 29760237 [PubMed - as supplied by publisher]
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research