Department of Biomedical Sciences, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea.
Cancer Lett. 2011 Jul 28;306(2):190-6. doi: 10.1016/j.canlet.2011.03.005. Epub 2011 Apr 3.
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-1α 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 cancer therapy against HCC.
肝细胞癌 (HCC) 是最常见的恶性肿瘤之一，但在有效的治疗方法上并没有重大进展。在这项研究中，HS-113 被合成一种新型化合物，N-(5-(2-溴苄基)噻唑-2-基)苯并呋喃-2-甲酰胺，并在人 HCC 细胞中检测其细胞毒性和抗癌作用。HS-113 以剂量依赖的方式强烈抑制 HCC 细胞的生长，通过增加亚 G1 凋亡细胞的比例诱导细胞凋亡，并导致细胞周期停滞在 G0/G1 期。此外，HS-113 增加了与细胞周期阻滞相关的 p27 的表达，降低了细胞周期蛋白 D1 的表达。通过 DAPI 和 TUNEL 染色证实了 HS-113 诱导的细胞凋亡，并观察到 PARP 和 caspase-3 的切割增加。此外，HS-113 降低了 HIF-1α 的蛋白表达和 VEGF 的分泌，并抑制了 HUVECs 的管形成。这些结果表明，HS-113 不仅抑制了细胞生长和血管生成，而且诱导了人 HCC 细胞的凋亡。我们认为，HS-113 可能是一种治疗 HCC 的潜在候选药物。
