Superoxide dismutase as a target enzyme for Fe-porphyrin-induced cell death.

The cell viability of human cancer cell lines treated with [5,10-bis(N-methyl-4-pyridyl)-15,20-diphenyl]porphinatoiron(III) (cis-FeMPy(2)P(2)P) has been estimated. The cis-FeMPy(2)P(2)P is a superoxide dismutase (SOD) mimic in vitro that exhibited a significant toxicity in cancer cell lines. This toxicity is rather due to pro-oxidant properties of the iron-porphyrin in vivo. We have demonstrated that there was the relationship between the LD(50) values calculated from the viability of cancer cell lines treated with cis-FeMPy(2)P(2)P and the SOD activities of the cell lines. Furthermore, the inhibition of SOD by antisense S-oligonucleotide increased the cytotoxic effect of cis-FeMPy(2)P(2)P against cancer cells. These results suggest that SOD is a target enzyme for the cell death induced by cis-FeMPy(2)P(2)P as a new class of anticancer agents.