A Novel Class I HDAC Inhibitor, AW01178, Inhibits Epithelial–Mesenchymal Transition and Metastasis of Breast Cancer

Author:

Liu Xiangxiang1,Chen Yawen2,Li Yang2,Shen Ying1,Dong Shasha1,Tan Jiang1

Affiliation:

1. The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China

2. The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China

Abstract

Epithelial–mesenchymal transition (EMT) refers to the transformation of polar epithelial cells into motile mesenchymal cells under specific physiological or pathological conditions, thus promoting the metastasis of cancer cells. Epithelial cadherin (E-cadherin) is a protein that plays an important role in the acquisition of tumor cell motility and serves as a key EMT epithelial marker. In the present study, AW01178, a small-molecule compound with potential therapeutic efficacy, was identified via in-cell Western high-throughput screening technology using E-cadherin as the target. The compound induced the upregulation of E-cadherin at both mRNA and protein levels and inhibited the EMT of breast cancer cells in vitro as well as metastasis in vivo. Mechanistically, AW01178 is a novel benzacetamide histone deacetylase inhibitor (HDACi) mainly targeting class I histone deacetylases. AW01178 promoted the transcription and expression of E-cadherin through enhancing the acetylation level of histone H3 in the E-cadherin promoter region, thereby inhibiting the metastasis of breast cancer cells. The collective findings support the potential utility of the novel HDACi compound identified in this study, AW01178, as a therapeutic drug for breast cancer and highlight its value for the future development of HDACi structures as anticancer drugs.

Funder

National Natural Science Foundation of China

Publisher

MDPI AG

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