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Novel BRD4-p53 Inhibitor SDU-071 Suppresses Proliferation and Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells.

Shumei WangKang LeiHsien-Tsung LaiTingting LiuLupei DuShwu-Yuan WuXiaohan YeCheng-Ming ChiangMingliang Yuan
Published in: ACS pharmacology & translational science (2024)
A promising alternative for cancer treatment involves targeted inhibition of the epigenetic regulator bromodomain-containing protein 4 (BRD4); however, available BRD4 inhibitors are constrained by their potency, oral bioavailability, and cytotoxicity. Herein, to overcome the drawback of the translational BRD4 inhibitors, we describe a novel BRD4-p53 inhibitor, SDU-071, which suppresses BRD4 interaction with the p53 tumor suppressor and its biological activity in MDA-MB-231 triple-negative breast cancer (TNBC) cells in vitro and in vivo. This novel small-molecule BRD4-p53 inhibitor suppresses cell proliferation, migration, and invasion by downregulating the expression of BRD4-targeted genes, such as c-Myc and Mucin 5AC, and inducing cell cycle arrest and apoptosis, as demonstrated in cultured MDA-MB-231 TNBC cells. Its antitumor activity is illustrated in an orthotopic mouse xenograft mammary tumor model. Overall, our results show that SDU-071 is a viable option for potentially treating TNBC as a new BRD4-p53 inhibitor.
Keyphrases
  • cell cycle arrest
  • cell death
  • pi k akt
  • signaling pathway
  • breast cancer cells
  • cell proliferation
  • small molecule
  • induced apoptosis
  • oxidative stress
  • cell cycle