Genistein induces apoptosis by down-regulating thioredoxin-1 in human hepatocellular carcinoma SNU-449 cells
- Authors
- Roh, Taylor; Kim, Sung Won; Moon, Soung Hoon; Nam, Myeong Jin
- Issue Date
- Nov-2016
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Genistein; Hepatocellular carcinoma; Apoptosis; Reactive oxygen species; Thioredoxin-1
- Citation
- FOOD AND CHEMICAL TOXICOLOGY, v.97, pp.127 - 134
- Journal Title
- FOOD AND CHEMICAL TOXICOLOGY
- Volume
- 97
- Start Page
- 127
- End Page
- 134
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7739
- DOI
- 10.1016/j.fct.2016.09.003
- ISSN
- 0278-6915
- Abstract
- 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. (C) 2016 Elsevier Ltd. All rights reserved.
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