Manganese superoxide dismutase negatively regulates the induction of apoptosis by 5-fluorouracil, peplomycin and gamma-rays in squamous cell carcinoma cells.
We investigated the relationship between manganese superoxide dismutase (Mn-SOD) activity and apoptosis induced by anticancer drugs and radiation. Although the activity of copper, zinc-SOD did not differ greatly among 9 squamous cell carcinoma (SCC) cell lines (OSC-1 to OSC-9), the Mn-SOD activity did differ among the cell lines. The Mn-SOD activity was increased by treatments with 5-fluorouracil (5-FU), peplomycin and 137Cs, reaching plateau levels at 12 h after treatment and then decreasing gradually. When OSC-1 and OSC-3, and OSC-2 and OSC-4 were examined as representative cell lines with low and high Mn-SOD activity, respectively, the decrease was more prominent in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The intracellular levels of superoxide and hydrogen peroxide (H2O2) were increased after treatment with the anticancer agents, and the increases were larger in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The decrease of mitochondrial membrane potential (deltapsi(m)) by the anticancer agents was marked in OSC-1 and OSC-3. Correspondingly, the release of cytochrome c, the activation of caspase-3 and the cleavage of poly(ADP-ribose)polymerase were stronger in OSC-3 than in OSC-4. In addition, apoptosis induced by the anticancer agents was prominent in OSC-3, exhibiting a close relationship with the deltapsi(m) and the H2O2 level. These results indicate that Mn-SOD in SCC cells modulates apoptosis induction and the inactivation of Mn-SOD might be a promising strategy for SCC treatment.
Ueta
E
E
Department of Oral Surgery, Kochi Medical School, Nankoku-city.
Yoneda
K
K
Yamamoto
T
T
Osaki
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D002470:Cell Survival / Q000187:drug effects; D005472:Fluorouracil / Q000627:therapeutic use; D005720:Gamma Rays; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D017663:Peplomycin / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism*
D000970:Antineoplastic Agents; D017663:Peplomycin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005472:Fluorouracil