-
Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization
-
Jin Ho Kim, Sung Ho Moon, Mina No, Jae Jin Kim, Eun Jung Choi, Bong Jun Cho, Jae Sung Kim, Il Han Kim, In Ah Kim
-
Cancer Res Treat. 2016;48(3):1130-1140. Published online November 17, 2015
-
DOI: https://doi.org/10.4143/crt.2015.206
-
-
 Abstract
 PDF Supplementary Material PubReader ePub
- Purpose
Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity. Materials and Methods Because pharmacologic HDAC inhibitors lack isotype-specificity, RNA interference against 11 HDAC isotypes was used to inhibit HDAC in an isotype-specific manner. Radiation cell survival was evaluated using a clonogenic assay in SQ20B cells transfected with small interfering RNA specifically targeting HDAC isotypes. Immunocytochemistry was performed for detection of γH2AX foci. Protein expression was measured using Western blotting.
Results
Among 11 HDAC isotypes tested, specific inhibition of 7 isotypes (HDAC1, HDAC3, HDAC4, HDAC6, HDAC7, HDAC10, and HDAC11) enhanced radiation lethality in SQ20B cells. Radiosensitization by inhibition of these HDAC isotypes was accompanied by delay of DNA double strand break repair. Radiosensitivity of SQ20B cells was not altered by selective inhibition of the remaining four isotypes (HDAC2, HDAC5, HDAC8, and HDAC9). Inhibition of HDAC isotypes resulted in downregulation of various proteins involved in pro-survival and DNA damage repair pathways. Conclusion Isotype-specificity exists in HDAC inhibition-induced radiosensitization. Different HDAC isotypes are differentially involved in modulation of cellular radiosensitivity.
-
Citations
Citations to this article as recorded by  - HDAC11: A novel target for improved cancer therapy
Yan Liu, Xuechao Tong, Weina Hu, Da Chen
Biomedicine & Pharmacotherapy.2023; 166: 115418. CrossRef - Histone deacetylase 10, a potential epigenetic target for therapy
Fajuan Cheng, Bin Zheng, Jianwei Wang, Guiting Zhao, Zhongshun Yao, Zhihong Niu, Wei He
Bioscience Reports.2021;[Epub] CrossRef - Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
Hoon Sik Choi, Jin Hyun Kim, Si Jung Jang, Jeong Won Yun, Ki Mun Kang, Hojin Jeong, In Bong Ha, Bae Kwon Jeong
Cancer Research and Treatment.2021; 53(3): 685. CrossRef - HDAC11: a rising star in epigenetics
Shan-Shan Liu, Fei Wu, Yue-Mei Jin, Wei- Qin Chang, Tian-Min Xu
Biomedicine & Pharmacotherapy.2020; 131: 110607. CrossRef - Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Research and Treatment.2019; 51(2): 696. CrossRef - Molecular imaging HDACs class IIa expression-activity and pharmacologic inhibition in intracerebral glioma models in rats using PET/CT/(MRI) with [18F]TFAHA
Maxwell T. Laws, Robin E. Bonomi, Swatabdi Kamal, David J. Gelovani, Jeremy Llaniguez, Shreya Potukutchi, Xin Lu, Thomas Mangner, Juri G. Gelovani
Scientific Reports.2019;[Epub] CrossRef - Mechanism of the Antitumor and Radiosensitizing Effects of a Manganese Porphyrin, MnHex-2-PyP
Sung-Won Shin, Changhoon Choi, Ga-Haeng Lee, Arang Son, Su-Hyeon Kim, Hee Chul Park, Ines Batinic-Haberle, Won Park
Antioxidants & Redox Signaling.2017; 27(14): 1067. CrossRef - MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H. Kim, David J Lee, In Ah Kim
Oncotarget.2017; 8(39): 65457. CrossRef - Targeting Histone Deacetylase 8 as a Therapeutic Approach to Cancer and Neurodegenerative Diseases
Alokta Chakrabarti, Jelena Melesina, Fiona R Kolbinger, Ina Oehme, Johanna Senger, Olaf Witt, Wolfgang Sippl, Manfred Jung
Future Medicinal Chemistry.2016; 8(13): 1609. CrossRef
-
12,320
View
-
153
Download
-
10
Web of Science
-
9
Crossref
|
KCA
