Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) play a role in the modulation of apoptosis. Antioxidant defence mechanisms against cell death involving apoptosis due to UVB irradiation were studied on three established cell lines (SCC derived from human skin squamous cell carcinoma, F-SV and F-ST derived from human skin fibroblasts) which were susceptible to cell death by UVB irradiation (12.5-250 mJ/cm2), and one cell line (N-F) derived from primary cultured human skin fibroblasts which was resistant to cell death. We compared antioxidant defences between the three established cell lines and N-F, measuring four antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) and a non-enzymatic antioxidant glutathione. The greatest difference was that Cu, Zn-SOD activity in N-F was 3-4-times the three other cell lines. Though SCC had much larger amounts of glutathione and higher antioxidant enzyme activities except for Cu, Zn-SOD than N-F, SCC was very susceptible to cell death. After UVB irradiation (at 16 h after 12.5 mJ/cm2), in all cell lines, SOD activity increased 1.1-1.3-times that of non-irradiated cells, while other enzyme activities remained constant. This presumably represents a protective response against ROS generated during UVB irradiation. N-F which was resistant to UVB-induced cell death had higher Cu, Zn-SOD activity before UVB irradiation, and a larger increase of SOD (mainly Mn-SOD) after UVB exposure than the other cell lines which were susceptible to cell death. Therefore, we conclude that the most important enzymatic antioxidant to protect cells from UVB damage is SOD.
 ...
PMID:Ultraviolet B-induced cell death in four cutaneous cell lines exhibiting different enzymatic antioxidant defences: involvement of apoptosis. 967 96

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.
 ...
PMID:Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and gamma-rays regulating expression of the BCL-2 family proteins, COX-2 and p21. 1174 42

Radiation therapy of tumors of the head and neck region is compromised by dose limiting toxicity of normal tissues including the oral cavity and oropharyngeal mucosa. MnSOD-Plasmid Liposome (MnSOD-PL) intraoral gene therapy has been demonstrated to decrease normal tissue toxicity and also improve survival in mice with orthotopic SCC-VII squamous cell tumors on the floor of the mouth. Furthermore, intravenous administration of MnSOD-PL in mice with orthotopic tumors, or addition of MnSOD-PL to tumor cell lines in vitro produces a radiosensitizing effect attributable to differences in antioxidant pool responses of tumor cells compared to normal tissues following irradiation. To determine whether EGF receptor (EGFR) antagonists Iressa, or Cetuximab provided further improvement of radiation killing of squamous cell tumors, MnSOD-PL transfected or control SCCVII tumor cells were irradiated in vitro, and then the effect of EGFR receptor antagonists was tested. Cells transfected with MnSOD-PL were relatively radiosensitive D0 = 1.244 +/- 0.126 Gy compared to control D0 = 3.246 +/- 0.087 (p < 0.0001). Clonogenic radiation survival curves of SCCVII cells demonstrated radiosensitization by Iressa D0 = 2.770 +/- 0.134 Gy (p = 0.0264), but no significant radiosensitizing effect of Cetuximab D0 = 3.193 +/- 0.309 (p = 0.7338). The combination of MnSOD-PL plus Iressa further increased radiosensitivity of SCC-VII cells in vitro D0 = 0.785 +/- 0.01064 (p < 0.0001). The results suggest some synergy of the effectiveness of the EGFR antagonist Iressa on increasing the radiation killing of SCC-VII cells that supplements MnSOD-PL tumor radiosensitization.
 ...
PMID:Effect of EGFR antagonists gefitinib (Iressa) and C225 (Cetuximab) on MnSOD-plasmid liposome transgene radiosensitization of a murine squamous cell carcinoma cell line. 1720 69

Intraoral manganese superoxide dismutase (SOD2)-plasmid liposome (PL) radioprotective gene therapy prolongs the survival of mice with orthotopic oral cavity tumors within the irradiated field. To determine whether the mechanism involved effects in antioxidant pool, C57BL/6J mice bearing orthotopic oral cavity squamous cell carcinoma SCC-VII tumors received intraoral or intravenous MnSOD-PL gene therapy 24 h prior to 18 Gy irradiation to the head and neck region. Glutathione (GSH) levels and levels of radiation-generated nitric oxide and peroxynitrite were measured in orthotopic tumors and in adjacent oral mucosa. MnSOD-PL transfection of the SCC-VII tumor cells, but not normal embryo fibroblasts, produced acute radiosensitization. Furthermore, SCC-VII tumor cells demonstrated increased relative hydrogen peroxide (the product of MnSOD superoxide dismutation)-induced apoptosis in vitro. Radiation decreased levels of GSH and increased GPX in both tumor and normal cells in vitro, effects that were blunted by MnSOD-PL treatment. In vivo irradiation decreased GSH and GPX more effectively in tumors, and the decrease was not reversed by MnSOD-PL therapy. Intravenous but not intraoral administration of epitope-tagged hemagglutinin MnSOD-PL resulted in significant uptake in orthotopic tumors and decreased the levels of radiation-induced nitric oxide and peroxynitrite. Thus normal tissue radioprotective MnSOD-PL gene therapy radiosensitizes tumor cell lines in vitro and has a therapeutic effect on orthotopic tumors in part through its effects on tumor antioxidants.
 ...
PMID:Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthotopic tumors. 1731 75