title: Fe-SOD cooperates with Nutlin3 to selectively inhibit cancer cells in vitro and in vivo.
abstract: Nutlin3, a non-genotoxic agonist of p53, is currently in phase II clinical trials for cancer treatment. However, its effects on normal tissues and cell types remain largely to be determined. Drugs that can selectively target cancer cells as well as cooperate with the p53 pathway are thus greatly needed. Iron-superoxide dismutase (Fe-SOD) is a potential candidate as it selectively targets cancer cells by eliminating the abnormally high levels of reactive oxygen species (ROS) in cancer cells; it also inhibits cancer cell growth by induction of p27. Here, we show evidence that modulating redox and ROS homeostasis cooperates with Nutlin3 to selectively inhibit cancer cells in vitro and in vivo. Co-treatment of Fe-SOD and Nutlin3 showed synergistic inhibition on cancer cells in vitro, and the induction of p27 appeared to be involved. No effects were observed on normal cells. In addition, such co-treatment further exhibited synergistic inhibition on tumor growth in vivo in a murine B16 xenograft model, while the individual treatments only achieved very limited inhibition. Thus, Fe-SOD cooperated with Nutlin3 to selectively inhibit cancer cells in vitro and in vivo.
authors: Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.
authors: Yong
authors: Y
authors: Qin
authors: Wei
authors: W
authors: Dai
authors: Yu
authors: Y
authors: Wang
authors: Xing-Guo
authors: XG
authors: Gong
authors: Min
authors: M
authors: Lu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008081:Liposomes; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D007093:Imidazoles; D008081:Liposomes; D010879:Piperazines; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; C482205:nutlin 3; D013482:Superoxide Dismutase