Genistein induces apoptosis by down-regulating thioredoxin-1 in human hepatocellular carcinoma SNU-449 cells.
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.
Department of Biological Science, Gachon University, 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 461-701, Republic of Korea.
Taylor
T
Roh
Department of Biological Science, Gachon University, 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 461-701, Republic of Korea.
Sung Won
SW
Kim
Department of Biological Science, Gachon University, 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 461-701, Republic of Korea.
Soung Hoon
SH
Moon
Department of Biological Science, Gachon University, 1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, 461-701, Republic of Korea. Electronic address: protein@gachon.ac.kr.
Myeong Jin
MJ
Nam
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013879:Thioredoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016588:Anticarcinogenic Agents; D017382:Reactive Oxygen Species; C491203:TXN protein, human; D013879:Thioredoxins; D019833:Genistein
Apoptosis; Genistein; Hepatocellular carcinoma; Reactive oxygen species; Thioredoxin-1