Downregulation of the Ca2+‐activated K+ channel KCa3.1 by histone deacetylase inhibition in human breast cancer cells. Issue 2 (17th March 2016)

• Record Type: Journal Article
• Authors: Ohya, Susumu; Kanatsuka, Saki; Hatano, Noriyuki; Kito, Hiroaki; Matsui, Azusa; Fujimoto, Mayu; Matsuba, Sayo; Niwa, Satomi; Zhan, Peng; Suzuki, Takayoshi; Muraki, Katsuhiko
• Is Part Of: Pharmacology research & perspectives. Volume 4:Issue 2(2016:Apr.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-03-17
• Subjects: Breast cancer -- Ca2+‐activated K+ channel -- histone deacetylase inhibitor -- vorinostat; Pharmacology -- Periodicals; Drug development -- Periodicals; 615.105
• DOI: 10.1002/prp2.228
• Languages: English
• ISSNs: 2052-1707

Abstract

Abstract: The intermediate‐conductance Ca 2+ ‐activated K + channel KC 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 (HDACis) have considerable potential for cancer therapy, however, the effects of HDACis on ion channel expression have not yet been investigated in detail. The results of this study showed a significant decrease in KC a 3.1 transcription by HDAC inhibition in the human breast cancer cell line YMB‐1, which functionally expresses KCa 3.1. A treatment with the clinically available, class I, II, and IV HDAC inhibitor, vorinostat significantly downregulated KC a 3.1 transcription in a concentration‐dependent manner, and the plasmalemmal expression of the KC a 3.1 protein and its functional activity were correspondingly decreased. Pharmacological and siRNA‐based HDAC inhibition both revealed the involvement of HDAC2 and HDAC3 in KC a 3.1 transcription through the same mechanism. The downregulation of KC 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, IGFBP5. The significant decrease in KC a 3.1 transcription by HDAC inhibition was also observed in the KC a 3.1‐expressing human prostate cancer cell line, PC‐3. These results suggest that vorinostat and the selective HDACis for HDAC2 and/or HDAC3 are effective drug candidates for KC a 3.1‐overexpressing cancers.