I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the acetylation of p53

Mei Yang; Xuefei Dang; Yue Tan; Meixing Wang; Xiaojing Li; Gang Li

doi:10.1016/j.biopha.2018.01.063

I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the acetylation of p53

Biomed Pharmacother. 2018 Mar:99:220-226. doi: 10.1016/j.biopha.2018.01.063.

Authors

Mei Yang¹, Xuefei Dang¹, Yue Tan¹, Meixing Wang¹, Xiaojing Li², Gang Li³

Affiliations

¹ Department of Medical Oncology, Brunch of MinHang, Fudan University Shanghai Cancer Hospital, Shanghai, 200240, China.
² Department of Medical Oncology, Fifth People's Hospital Affiliated to Fudan University, Shanghai, 200240, China.
³ Department of Medical Oncology, Brunch of MinHang, Fudan University Shanghai Cancer Hospital, Shanghai, 200240, China. Electronic address: pf_gangli@163.com.

PMID: 29334665
DOI: 10.1016/j.biopha.2018.01.063

Abstract

Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids. The up-regulated acetylation of p53 promoted the transcriptional activity of p53 and induced the expression of p21, which consequently caused cell cycle arrest at G1 phase. Administration of I-7ab inhibited the colony formation of TNBC cells. Collectively, these results indicated I-7ab as a promising anti-cancer agent in the treatment of TNBC.

Keywords: Cell apoptosis; Cell cycle arrest; HDAC3; I-7ab; TNBC; p53.

MeSH terms

Acetylation
Apoptosis / drug effects
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Female
Gene Expression Regulation, Neoplastic / drug effects
Histone Deacetylase 3
Histone Deacetylases / metabolism*
Humans
Hydroxamic Acids / pharmacology*
Quinolines / pharmacology*
Transcription, Genetic / drug effects
Triple Negative Breast Neoplasms / enzymology*
Triple Negative Breast Neoplasms / genetics
Triple Negative Breast Neoplasms / pathology*
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*

Substances

Cyclin-Dependent Kinase Inhibitor p21
Histone Deacetylases
Hydroxamic Acids
Quinolines
Tumor Suppressor Protein p53
Histone Deacetylase 3
N-hydroxy-3-(2-phenyl-4-((2-(piperidin-1-yl)ethyl)amino)-2H-pyrazolo(3,4-c)quinolin-8-yl)acrylamide