Superoxide dismutase induces G1-phase cell cycle arrest by down-regulated expression of Cdk-2 and cyclin-E in murine sarcoma S180 tumor cells.
As an efficient reactive oxygen species-scavenging enzyme, superoxide dismutase (SOD) has been shown to inhibit tumor growth and interfere with motility and invasiveness of cancer cells. In this study, the molecular mechanisms of cell cycle arrest when S180 tumor cells were exposed to high levels of SOD were investigated. Here, both murine sarcoma S180 tumor cells and NIH-3T3 mouse fibroblasts were respectively treated with varying concentrations of Cu/Zn-SOD for 24, 48 and 72 h to determine optimal dose of SOD, which was a concentration of 800 U/ml SOD for 48 h. It is found that SOD induced S180 cell cycle arrest at G1-phase with decreasing level of superoxide production, whereas SOD had less effect on proliferation of NIH-3T3 cells. Moreover, the expression rate of Proliferating Cell Nuclear Antigen (PCNA) in S180 tumor cells was suppressed after SOD treatment, which indicated the inhibition of DNA synthesis in S180 cells. Besides, there were significant down-regulations of cyclin-E and Cdk-2 in S180 cells after SOD treatment, which contributed to the blockage of G1/S transition in S180 cell cycle. Together, our data confirmed that SOD could notably inhibit proliferation of S180 tumor cell and induce cell cycle arrest at G1-phase by down-regulating expressions of cyclin-E and Cdk-2.
Tianjin University of Science and Technology, Key Laboratory of Food Nutrition and Safety, Ministry of Education, Institute of Food Engineering and Biotechnology, Tianjin, China.
Dongyue
D
Liu
Anjun
A
Liu
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D041681:NIH 3T3 Cells; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D019927:Cyclin E; D018809:Proliferating Cell Nuclear Antigen; D013482:Superoxide Dismutase; D051357:Cyclin-Dependent Kinase 2