Manganese Superoxide Dismutase Negatively Regulates the Induction of Apoptosis by 5‐Fluorouracil, Peplomycin and γ‐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 (137)Cs, 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 (H(2)O(2)) were increased after treatment with the anti‐cancer 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 (Δψ(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 Δ7psi;(m) and the H(2)O(2) 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.