Mimic of manganese superoxide dismutase to induce apoptosis of human non-Hodgkin lymphoma Raji cells through mitochondrial pathways.
Increased reactive oxygen species (ROS) such as superoxide have been implicated as causal elements of oncogenesis. A variety of cancers have displayed changes in steady-state levels of key antioxidant enzymes, with the mitochondrial form of superoxide dismutase (MnSOD) being commonly implicated. Increasing MnSOD expression suppresses the malignant phenotype in various cancer cell lines and suppresses tumor formation in xenograft and transgenic mouse models. In this study, we examined the anti-proliferation effect of mimic of manganese superoxide dismutase (MnSODm) on human non-Hodgkin lymphoma Raji cells. The results showed that MnSODm significantly reduced the proliferation of Raji cells in a concentration and a time-dependent manner. By flow cytometric analysis, we found that MnSODm treatment resulted in an increased apoptosis in Raji cells. MnSODm also increased the production of ROS and the expression levels of cleaved caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and Bax in Raji cells. Moreover, the expression of Bcl-2 protein showed down-regulation in the MnSODm treatment group. In addition, MnSODm significantly elevated the level of cytochrome c in cytosol. These findings suggest that the activation of the mitochondrial pathway is involved in MnSODm-induced apoptosis in Raji cells.
Department of Pharmacy, People's Hospital of Gansu Province, Lanzhou 730000, Gansu, China.
Yan-Hong
YH
Wang
Xiao-Lai
XL
Yang
Xia
X
Han
Ling-Fang
LF
Zhang
Hong-Ling
HL
Li
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D013482:Superoxide Dismutase; D053148:Caspase 3