Food & Chemical Toxicology, 2016, 97:127-134.

Genistein induces apoptosis by down-regulating thioredoxin-1 in human hepatocellular carcinoma SNU-449 cells

Taylor Roh, Sung Won Kim, Soung Hoon Moon, et al

Department of Biological Science, Gachon University, 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 461-701, Republic of Korea

Genistein (GEN), a natural isoflavonoid phytoestrogen, has anti-cancer activity against various types of cancers. However, GEN has not been thoroughly investigated in human hepatocellular carcinoma cells. In this study, we evaluated the anti-cancer effects of GEN on SNU-449 cells. GEN inhibited the proliferation of SNU-449 cells in a concentration-dependent manner. We observed the typical characteristics of apoptosis, such as DNA fragmentation and caspase-3 activation. To identify proteins related to GEN-induced apoptosis, we performed two-dimensional electrophoresis and identified differentially expressed proteins. Proteomic analysis showed that the antioxidant protein thioredoxin-1 was associated with GEN-induced apoptosis. GEN treatment decreased thioredoxin-1 levels and increased intracellular accumulation of reactive oxygen species. In addition, GEN activated apoptosis signal-regulating kinase 1, c-Jun N-terminal kinases (JNK) and p38. We also observed that pretreatment with the JNK and p38 inhibitors (SP600125 and SB203580) decreased GEN-induced cell death. These results indicate that GEN has potential antitumor effects against SNU-449 cells through the down-regulation of thioredoxin-1.

英国《食品化学毒理学》, 2016, 97:127-134.

染料木黄酮通过下调人肝细胞癌SNU-449细胞中的硫氧还蛋白-1诱导细胞凋亡

Taylor Roh, Sung Won Kim, Soung Hoon Moon, et al

生物科学系，加拿大大学，1342，Seongnam-daero，Seongnam-gu，Seongnam-si，Gyeonggi-do，461-701，大韩民国

染料木素（genistein）（天然异黄酮植物雌激素）具有抗各种癌症的抗癌活性。然而，GEN尚未在人肝细胞癌细胞中进行彻底研究。在这项研究中，我们评估了GEN对SNU-449细胞的抗癌作用。 GEN以浓度依赖性方式抑制SNU-449细胞的增殖。我们观察到凋亡的典型特征，例如DNA片段化和半胱天冬酶-3激活。为了鉴定与GEN诱导的凋亡相关的蛋白质，我们进行二维电泳并鉴定差异表达的蛋白质。蛋白质组学分析表明，抗氧化蛋白硫氧还蛋白-1与GEN诱导的凋亡有关。 GEN处理降低硫氧还蛋白-1水平和增加细胞内积累的活性氧。此外，GEN激活细胞凋亡信号调节激酶1，c-Jun N-末端激酶（JNK）和p38。我们还观察到用JNK和p38抑制剂（SP600125和SB203580）的预处理降低了GEN诱导的细胞死亡。这些结果表明GEN通过下调硫氧还蛋白-1对SNU-449细胞具有潜在的抗肿瘤作用。