Open AccessDownregulation of the Ca 2+ ‐activated K + channel K C a 3.1 by histone deacetylase inhibition in human breast cancer cells
Author(s) -
Ohya Susumu,
Kanatsuka Saki,
Hatano Noriyuki,
Kito Hiroaki,
Matsui Azusa,
Fujimoto Mayu,
Matsuba Sayo,
Niwa Satomi,
Zhan Peng,
Suzuki Takayoshi,
Muraki Katsuhiko
Publication year - 2016
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.228
Subject(s) - vorinostat , histone deacetylase , downregulation and upregulation , gene silencing , cancer research , chemistry , transcription factor , cancer cell , microbiology and biotechnology , biology , cancer , histone , medicine , biochemistry , gene
The intermediate‐conductance Ca 2+ ‐activated K + channel K C a 3.1 is involved in the promotion of tumor growth and metastasis, and is a potential therapeutic target and biomarker for cancer. Histone deacetylase inhibitors ( HDAC is) have considerable potential for cancer therapy, however, the effects of HDAC is on ion channel expression have not yet been investigated in detail. The results of this study showed a significant decrease in K C a 3.1 transcription by HDAC inhibition in the human breast cancer cell line YMB ‐1, which functionally expresses K Ca 3.1. A treatment with the clinically available, class I, II , and IV HDAC inhibitor, vorinostat significantly downregulated K C a 3.1 transcription in a concentration‐dependent manner, and the plasmalemmal expression of the K C a 3.1 protein and its functional activity were correspondingly decreased. Pharmacological and si RNA ‐based HDAC inhibition both revealed the involvement of HDAC 2 and HDAC 3 in K C a 3.1 transcription through the same mechanism. The downregulation of K C a 3.1 in YMB ‐1 was not due to the upregulation of the repressor element‐1 silencing transcription factor, REST and the insulin‐like growth factor‐binding protein 5, IGFBP 5. The significant decrease in K C a 3.1 transcription by HDAC inhibition was also observed in the K C a 3.1‐expressing human prostate cancer cell line, PC ‐3. These results suggest that vorinostat and the selective HDAC is for HDAC 2 and/or HDAC 3 are effective drug candidates for K C a 3.1‐overexpressing cancers.