Research Papers:
A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma
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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: [email protected]
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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