A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma
Year: 2016
Type: article
Abstract: // Seung Ah Choi 1, 2 , Pil Ae Kwak 1, 2 , Chul-Kee Park 3 , Kyu-Chang Wang 1, 3 , Ji Hoon Phi 1, 2, 3 , Ji Yeoun Lee 1, 3, 4 , Chang Sik Lee 5 , Ju-Hee Lee 5 , Seung-Ki Kim 1, 2, 3 1 Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul, Korea 2 Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea 3 Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea 4 Department of Anatomy, Seoul National University Hospital, Seoul, Korea 5 Chong 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.
Source: Oncotarget
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2549648494