Oncotarget

Research Papers:

A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma

Seung Ah Choi, Pil Ae Kwak, Chul-Kee Park, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Chang Sik Lee, Ju-Hee Lee and Seung-Ki Kim _

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Oncotarget. 2017; 8:9123-9133. https://doi.org/10.18632/oncotarget.13265

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Abstract

Seung Ah Choi1,2, Pil Ae Kwak1,2, Chul-Kee Park3, Kyu-Chang Wang1,3, Ji Hoon Phi1,2,3, Ji Yeoun Lee1,3,4, Chang Sik Lee5, Ju-Hee Lee5, Seung-Ki Kim1,2,3

1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul, Korea

2Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea

3Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea

4Department of Anatomy, Seoul National University Hospital, Seoul, Korea

5Chong Kun Dang Research Institute, CKD Pharmaceuticals, Gyeonggi-do, Korea

Correspondence to:

Seung-Ki Kim, email: nsthomas@snu.ac.kr

Keywords: epigenetics, histone deacetylase inhibitor, glioblastoma

Received: May 09, 2016     Accepted: November 01, 2016     Published: November 10, 2016

ABSTRACT

There have been extensive efforts to improve the outcome of glioblastoma, but the prognosis of this disease has not been significantly altered to date. Histone deacetylase inhibitors (HDACIs) have been evaluated as promising anti-cancer drugs and regulate cell growth, cell cycle arrest and apoptosis in glioblastoma. Here, we demonstrated the therapeutic efficacy of a novel pan-HDACI, 7-ureido-N-hydroxyheptanamide derivative (CKD5), compared with traditional pan-HDACIs, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), in vitro and in vivo. Compared with SAHA and TSA, CKD5 had improved cytotoxic effects and induced apoptosis, anti-proliferative activity and cell cycle arrest at G2/M phase. Furthermore, CKD5 significantly reduced tumor volume and prolonged the survival in vivo compared with TSA, suggesting improved anti-cancer efficacy among HDACIs. Our results demonstrate that the novel HDACI CKD5 is a promising therapeutic candidate for glioblastoma.


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