The HDAC inhibitor HFY-4A improves TUSC2 transcription to induce immunogenic cell death in breast cancer

We managed to explore the function of HFY-4A, a novel histone deacetylases (HDACs) inhibitor, on breast Cancer as well as its potential mechanisms. MCF7 and T47D cells were treated with 0.8, 1.6 or 3.2 μM HFY-4A for 0-72 h, following of which CCK-8, colony formation, EdU staining, flow cytometry, Transwell, and wound healing assays were carried out. Western blot, immunohistochemistry, and ELISA were conducted for assaying the expression of immunogenic cell death (ICD)-related proteins. The interaction between HFY-4A, HDAC1, and tumor suppressor candidate 2 (TUSC2) was evaluated by chromatin immunoprecipitation assay. Further, the function of HFY-4A in breast Cancer progression in vivo was evaluated using xenograft mouse models. HFY-4A inhibited the proliferation, migration, and invasion, and induced Apoptosis of breast Cancer cells in a dose-dependent manner. HFY-4A dose-dependently caused the ICD of breast Cancer cells, as evidenced by the significant high levels of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), and HSP90. Interestingly, HFY-4A could facilitate TUSC2 transcription by promoting acetylation of histones on the TUSC2 promoter. The results of rescue assays revealed that HFY-4A repressed proliferation and mobility, but enhanced Apoptosis and ICD through facilitating TUSC2 transcription in breast Cancer. In breast Cancer xenograft mouse models, HFY-4A was verified to inhibit tumor growth via upregulating TUSC2. HFY-4A could inhibit breast Cancer cell proliferation and mobility, and enhanced Apoptosis and ICD through facilitating TUSC2 transcription.

Breast cancer; HDAC; HFY-4A; ICD; TUSC2 transcription.