- ENGLISH
- P-ISSN3022-6805
- E-ISSN3022-6791
- KCI
BRD4 Inhibitor OPT-0010 Exerts Anticancer Effects Through Cell Cycle Arrest and Apoptotic Cell Death in Hepatic Carcinoma Cells
AlaAiob (Seoul National University Bundang Hospital, Seoul National University College of Medicine)
WooYeonHwang (Kyung Hee University College of Medicine)
DongHoonSuh (Seoul National University Bundang Hospital, Seoul National University College of Medicine)
KidongKim (Seoul National University Bundang Hospital, Seoul National University College of Medicine)
JaeHongNo (Seoul National University Bundang Hospital, Seoul National University College of Medicine)
Hye-YeounKang (JBK-LAB, Inc.)
HyeWonJeon (Seoul Metropolitan Boramae Medical Center)
YongBeomKim (Seoul National University Bundang Hospital, Seoul National University College of Medicine)
초록
초록 국문
- keywords
- 키워드1, 키워드2
Abstract
Objective: Bromodomain-containing protein 4 (BRD4) is a critical transcriptional regulator of cell growth and differentiation. BRD4 inhibitors have the potential to curb cancer cell proliferation by downregulating the expression of associated genes. This study investigated the anticancer effects of a novel BRD4 inhibitor, OPT-0010, on human hepatic carcinoma cell lines. Materials and Methods: Two hepatic carcinoma cell lines, SK-Hep1 and Huh-7, were subjected to 48-h OPT-0010 treatment. Cell viability and proliferation were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and adenosine triphosphate assays, respectively. Flow cytometry was used to detect cell cycle arrest. Apoptotic cell death was evaluated using Annexin V and caspase 3 assays. BRD4 and apoptosis-related genes (e.g., BCL2 and BAX) and proteins (e.g., cleaved caspase-3, cleaved PARP, and BCL2) were evaluated using real-time polymerase chain reaction and western blotting, respectively. Additionally, a mouse xenograft model was used to analyze tumor growth, weight, and messenger RNA (mRNA) levels. Results: OPT-0010 significantly decreased cell viability and proliferation, inducing cell cycle arrest and apoptotic cell death in both SK-Hep1 and Huh-7 cell lines. OPT-0010 showed substantial anti-tumor efficacy in a mouse xenograft model, affecting tumor growth and the expression of BRD4 and apoptosis-related proteins. Furthermore, in synergy with sorafenib, OPT-0010 exhibited an enhanced effect, increasing apoptotic cell death, and effectively suppressing tumor growth in vitro and in vivo. Conclusion: This study provided comprehensive insights into the mechanisms and therapeutic effects of OPT-0010 on human hepatic carcinoma cell lines and in vivo mouse xenograft models. These results suggest that OPT-0010 is a promising therapeutic agent for treating human hepatocellular carcinoma.
- keywords
- BRD4 inhibitor, OPT-0010, hepatic carcinoma, cell viability, apoptosis, tumor growth, synergistic effect
- 투고일Received
- 2025-04-14
- 수정일Revised
- 2025-05-23
- 게재확정일Accepted
- 2025-05-26
- 출판일Published
- 2025-05-30
- 다운로드 수
- 조회수
- 0KCI 피인용수
- 0WOS 피인용수