title: Anti-proliferative effects of recombinant iron superoxide dismutase on HepG2 cells via a redox-dependent PI3k/Akt pathway.
abstract: The coding sequence for an iron superoxide dismutase (fe-sod) was amplified from the Nostoc commune genome. Recombinant Fe-SOD was overexpressed in Escherichia coli, accounting for approximately 76% of total bacterial protein. Fe-SOD was purified from bacterial lysate by Ni-NTA column chromatography and used to generate an anti-SOD antibody. The purified Fe-SOD was encapsulated in liposomes and delivered to HepG2 liver tumor cells to eliminate cellular superoxide anions. The SOD-loaded cells exhibited lower reactive oxygen species (ROS) levels and higher reduced glutathione (GSH) levels. In Fe-SOD-treated cells, the cell cycle was delayed in the G(1) phase, and HepG2 cell growth slowed in association with dephosphorylation of the serine-threonine kinase Akt. Low-dose H(2)O(2) stimulated Akt phosphorylation, implying that Akt activation in HepG2 cells is redox-sensitive. Akt phosphorylation was abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitors, suggesting that PI3K is an upstream mediator of Akt activation in HepG2 cells. This study provides insight into recombinant Fe-SOD-induced signaling mechanisms in liver tumor cells and suggests the feasibility of using Fe-SOD as an antitumor agent.
authors: Institute of Biochemistry, Zhejiang University, Hangzhou, People's Republic of China.
authors: Min
authors: M
authors: Lu
authors: Chong-Shan
authors: CS
authors: Bi
authors: Xing-Guo
authors: XG
authors: Gong
authors: Han-Min
authors: HM
authors: Chen
authors: Xie-Huang
authors: XH
authors: Sheng
authors: Tong-le
authors: TL
authors: Deng
authors: Ke-di
authors: KD
authors: Xu
mesh_terms: D045744:Cell Line, Tumor / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D050501:Nostoc commune / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013482:Superoxide Dismutase