Role of NADPH Oxidase in the Mechanism of Arachidonic Acid-induced Apoptosis in HepG2 Human Hepatoblastoma Cells

HepG2 간암세포에서 아라키돈산에 의한 세포사멸기전에 미치는 NADPH 산화효소의 역할

  • 남정원 (덕성여자대학교 약학대학) ;
  • 이용수 (덕성여자대학교 약학대학)
  • Received : 2011.12.26
  • Accepted : 2012.01.09
  • Published : 2012.04.30

Abstract

Previously, we have reported that arachidonic acid (AA) appears to be involved in the induction of apoptosis in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of the NADPH oxidase, a membranebound enzyme generating reactive oxygen species (ROS), in the mechanism of AA-induced apoptosis in HepG2 cells. Apoptotic cell death induced by AA was significantly suppressed by various inhibitors of the NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP). In addition, these inhibitors of the NADPH oxidase completely blunted the AA-induced ROS elevation. Next, we investigated the implication of metabolic pathway of AA in these AA actions. Both apoptosis and ROS production induced by AA were not significantly altered by treatment with indomethacin (Indo) or nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively, suggesting that AA metabolites produced by COX or LOX may not have an essential role in the AA-induced apoptosis and ROS generation. Collectively, these results suggest that the NADPH oxidase may be a key player in the mechanism of AA-induced apoptosis in HepG2 cells. These results further suggest that NADPH oxidase may be a good target for the management of human hepatomas.

Keywords

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