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A novel histone deacetylases inhibitor exerts promising anti-breast cancer activity via triggering AIFM1-dependent programmed necrosis

ABSTRACT: Breast cancer is one of the most lethal cancers in women, and its resistance to chemotherapy remains a challenging problem. Histone deacetylases inhibitors (HDACIs) are a promising therapeutic tool for breast cancer. Here, we screened a library of synthetic small molecules and identified a novel HDACi, YF349, which possessed promising anti-breast cancer ability both in vitro and in vivo. Molecular and biochemical studies demonstrated that YF349 significantly increased the mRNA level of apoptosis-inducing factor (AIFM1) by blocking the binding of HDAC1 to the AIFM1 promoter. Further study revealed that YF349 significantly induced nuclear translocation of AIFM1 and promoted the formation of the AIF-CypA-gH2Ax complex in the nuclei, finally inducing AIF-mediated necrosis. Our finding suggests that AIFM1 can be explored as a molecular target in breast cancer and that targeting the HDAC1-AIFM1-CypA-gH2Ax signaling axis by YF349 may be a promising therapeutic strategy for breast cancer. We identified a novel compound for breast cancer therapy

ORGANISM(S): Homo sapiens

PROVIDER: GSE203025 | GEO | 2022/11/16

REPOSITORIES: GEO

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