Anti-cancer effects of a novel compound HS-113 on cell growth, apoptosis, and angiogenesis in human hepatocellular carcinoma cells
Anti-cancer effects of a novel compound HS-113 on cell growth, apoptosis, and angiogenesis in human hepatocellular carcinoma cells
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DOI：
10.1016/j.canlet.2011.03.005
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发表时间：
2011-07-28
期刊：
影响因子：
9.7
通讯作者：
Hong, Soon-Sun
中科院分区：
文献类型：
--
作者：
Choi, Myung-Joo;Jung, Kyung Hee;Hong, Soon-Sun
肝细胞癌（HCC）是最常见的恶性肿瘤之一，但有效的治疗方法尚未取得重大进展。本研究HS-113是一种新化合物。本文研究了N-（5-（2-溴苄基）噻唑-2-基）苯并呋喃-2-甲酰胺及其对人肝癌细胞的细胞毒活性和抗癌作用。HS-113以剂量依赖方式强烈抑制HCC细胞的生长，通过增加亚G1期凋亡细胞的比例诱导凋亡，并使细胞周期停滞在G 0/G1期。Also. HS-113可增加p27的表达，降低cyclin D1的表达，使细胞周期阻滞。DAPI和TUNEL染色证实HS-113诱导的细胞凋亡，并观察到裂解的PARP和caspase-3的增加。HS-113还可抑制HUVECs中HIF-1 α的蛋白表达和VEGF的分泌，抑制HUVECs管腔形成。结果表明，HS-113不仅抑制细胞生长和血管生成，而且诱导人肝癌细胞凋亡。我们认为HS-113可能是一种潜在的肝癌治疗药物。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Hepatocellular carcinoma (HCC) is one of the most common malignancies, yet there have been no significant advances in effective therapeutics. In this study. HS-113 was synthesized as a novel compound. N-(5-(2-bromobenzyl) thiazole-2-yl) benzofuran-2-carboxamide and its cytotoxic activity and anti-cancer effect were examined in human HCC cells. HS-113 strongly suppressed growth of HCC cells in a dose-dependent manner, induced apoptosis by increasing the proportion of sub-G1 apoptotic cells, and caused cell cycle arrest at G0/G1 phase. Also. HS-113 increased the expression of p27 and decreased that of cyclin D1 associated with cell cycle arrest. Apoptosis by HS-113 was confirmed by DAPI and TUNEL staining, and the increases of the cleaved PARP and caspase-3 were observed. Furthermore, HS-113 decreased protein expression of HIF-1 alpha and secretion of VEGF, and inhibited the tube formation of HUVECs. These results showed that HS-113 not only inhibited cell growth and angiogenesis, but also induced apoptosis of human HCC cells. We suggest that HS-113 may be a potential candidate for caner therapy against HCC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.