A novel chalcone-based molecule, BDP inhibits MDA-MB-231 triple-negative breast cancer cell growth by suppressing Hsp90 function

摘要

Triple-negative breast cancer (TNBC) is a molecularly diverse and heterogeneous disease and the molecular heterogeneity of TNBC increases the difficulty in improving survival rates. To date, therapeutic approaches for the treatment of TNBC such as hormonal chemotherapy and trastuzumab-based therapy have been limited by the lack of target receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2), emphasizing the urgent need for identifying new therapeutic options. In this regard, heat shock protein 90 (Hsp90) has emerged as an attractive therapeutic target for TNBC. Hsp90 plays a central role in regulating correct folding, stability, and function of numerous oncogenic proteins. In the present study, we evaluated the in vitro effect of a small molecule Hsp90 inhibitor, (E)-3-(2-bromo-3,4,5-trimethoxyphenyl)-1-(2,4-dihydroxyphenyl) prop-2-en-1-one (BDP) on TNBC cell line, MDA-MB-231. This study indicated that BDP efficiently inhibited the growth of MDA-MB-231 cells in a dose-and time-dependent manner. BDP induced overall degradation of multiple oncogenic proteins including EGFR, Her2, Met, Akt, c-Raf, and Cdk4, consequently leading to apoptotic cell death. The flow cytometric analysis revealed that BDP promoted cell cycle arrest at G(2)/M phases. Moreover, BDP treatment attenuated the migration of MDA-MB-231 cells and impaired MMP9 activity, which are essential processes for tumor metastasis. Collectively, BDP represents a new class of Hsp90 inhibitor and shows therapeutic potential for TNBC treatment.