title: Inhibitory effect on the proliferation of human heptoma induced by cell-permeable manganese superoxide dismutase.
abstract: Mitochondrial antioxidant manganese superoxide dismutase (MnSOD) belongs to a group of genes whose expression is generally decreased significantly in patients with hepatoma. The proliferation of cancer cells with low expression of MnSOD exhibit high sensitivity to the elevated expression of MnSOD. However, due to the lack of ability to penetrate the cell membrane, the direct use and study of SOD for cancer treatment are largely hampered. In this work, cell penetrating peptide TAT was fused to the N-terminus of MnSOD to facilitate the penetration of MnSOD through cell membranes. Results showed that TAT-MnSOD wt treatment induced evident inhibitory effect on the proliferation of heptoma, with minimal effect on normal cells. It was further demonstrated that both the penetration of cells and enzymatic activity of MnSOD are essential to its inhibitory function, because only TAT-MnSOD wt, not inactive TAT-MnSOD mutant or MnSOD could successfully inhibit cell proliferation and reduce the intra-celluar reactive oxygen species (ROS). In addition, the lower oxidative stress delayed the cell cycle at G2/M and significantly slowed HepG2 cell growth in association with the dephosphorylation of survivin. Our results help in understanding the regulatory effects of MnSOD on cell viability and redox homestasis of heptoma and promise potential applications of TAT-MnSOD wt for clinical cancer therapy.
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors: Hua
authors: H
authors: Guo
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors: Na
authors: N
authors: Zhang
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors: Di
authors: D
authors: Liu
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China. Electronic address: pwang11@ecust.edu.cn.
authors: Ping
authors: P
authors: Wang
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China. Electronic address: maxy@ecust.edu.cn.
authors: Xingyuan
authors: X
authors: Ma
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000517:prevention & control; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D061986:MCF-7 Cells; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D013482:Superoxide Dismutase
keywords: P-survivin (Thr34); ROS; Redox homeostasis; TAT-MnSOD