BRD4 Inhibitor OPT-0010 Exerts Anticancer Effects Through Cell Cycle Arrest and Apoptotic Cell Death in Hepatic Carcinoma Cells

• 발행기관: 셀메드 세포교정의약학회
• 저자명: Bong-Keun Jang Ala Aiob Woo Yeon Hwang Dong Hoon Suh Kidong Kim Jae Hong No Hye-Yeoun Kang Hye Won Jeon Yong Beom Kim
• 간행물 정보: 『셀메드』Volume 15 Issue 6, 7~19쪽, 전체 13쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.05.31

국문 초록

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.

목차

INTRODUCTION

MATERIALS AND METHODS

RESULT

DISCUSSION

ACKNOWLEDGEMENT

RESEARCH FUNDING

CONFLICT OF INTEREST

EFERENCES

키워드

BRD4 inhibitor OPT-0010 hepatic carcinoma cell viability apoptosis tumor growth synergistic effect