TY - JOUR
T1 - Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1
AU - Wang, Ying
AU - Lonard, David M.
AU - Yu, Yang
AU - Chow, Dar Chone
AU - Palzkill, Timothy G.
AU - Wang, Jin
AU - Qi, Ruogu
AU - Matzuk, Alexander J.
AU - Song, Xianzhou
AU - Madoux, Franck
AU - Hodder, Peter
AU - Chase, Peter
AU - Griffin, Patrick R.
AU - Zhou, Suoling
AU - Liao, Lan
AU - Xu, Jianming
AU - O'malley, Bert W.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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 composed 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 that 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.
AB - 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 composed 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 that 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.
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U2 - 10.1158/0008-5472.CAN-13-2939
DO - 10.1158/0008-5472.CAN-13-2939
M3 - Article
C2 - 24390736
AN - SCOPUS:84896517086
SN - 0008-5472
VL - 74
SP - 1506
EP - 1517
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -