title: Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells.
abstract: This study investigates the role of the antioxidant enzyme manganese superoxide dismutase (MnSOD) in androgen-independent human prostate cancer (PC-3) cells' growth rate in vitro and in vivo. MnSOD levels were found to be lower in parental PC-3 cells compared to nonmalignant, immortalized human prostate epithelial cells (P69SV40T). To unravel the role of MnSOD in the prostate cancer phenotype, PC-3 cells were stably transfected with MnSOD cDNA plasmid. The MnSOD protein and activity levels in clones overexpressing MnSOD were increased seven- to eightfold. These cell lines showed elongated cell doubling time, reduced anchorage-independent growth in soft agar compared to parental PC-3 (Wt) cells, and reduced growth rate of PC-3 tumor xenografts in athymic nude mice. Flow cytometric studies showed an increase in membrane potential in the MnSOD-overexpressing clone (Mn32) compared to Wt and Neo cells. Also, production of extracellular H(2)O(2) was increased in the MnSOD-overexpressing clones. As determined by DNA cell cycle analysis, the proportion of cells in G(1) phase was enhanced by MnSOD overexpression. Therefore, MnSOD not only regulates cell survival but also affects PC-3 cell proliferation by retarding G(1) to S transition. Our results are consistent with MnSOD being a tumor suppressor gene in human prostate cancer.
authors.affiliation: Free Radical and Radiation Biology Program -- ESR Facility, University of Iowa, Iowa City, IA 52242-1101, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Venkataraman
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.forename: Christine
authors.initials: C
authors.lastname: Weydert
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Prabhat C
authors.initials: PC
authors.lastname: Goswami
authors.forename: Justine M
authors.initials: JM
authors.lastname: Ritchie
authors.forename: Larry W
authors.initials: LW
authors.lastname: Oberley
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase