Bufalin is a potent small molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1

By Ying Wang, D. Lonard, Yang Yu, D. Chow, Timothy G. Palzkill, Jin Wang, R. Qi, Alexander J. Matzuk, Xianzhou Song, Franck Madoux and 7 more. 2014

159 citations recorded by the source corpus.

Virtually all transcription factors partner with coactivators that recruit chromatin remodeling factors and interact with the basal transcription machinery. Coactivators have been implicated in cancer cell proliferation, invasion and metastasis, including the p160 steroid receptor coactivator (SRC) family comprised of SRC-1 (NCOA1), SRC-2 (TIF2/GRIP1/NCOA2), and SRC-3 (AIB1/ACTR/NCOA3). Given their broad involvement in many cancers, they represent candidate molecular targets for new chemotherapeutics. Here we report on the results of a high throughput screening effort which identified the cardiac glycoside bufalin as a potent small molecule inhibitor for SRC-3 and SRC-1. Bufalin strongly promoted SRC-3 protein degradation and was able to block cancer cell growth at nanomolar concentrations. When incorporated into a nanoparticle delivery system, bufalin was able to reduce tumor growth in a mouse xenograft model of breast cancer. Our work identifies bufalin as a potentially broad-spectrum small molecule inhibitor for cancer.

Subfields: Genetics, Molecular Biology, Oncology

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In Genetics

  1. Zhaohui S. Qin

In Molecular Biology

  1. Zhaohui S. Qin
  2. Yun Bai
  3. Rendong Yang
  4. Tianwei Yu

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