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.
Asayama
Shoichiro
S
Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan. asayama-shoichiro@c.metro-u.ac.jp
Kasugai
Nobuyoshi
N
Kubota
Sunao
S
Nagaoka
Shoji
S
Kawakami
Hiroyoshi
H
D001483:Base Sequence; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000737:chemistry; D008665:Metalloporphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018716:Molecular Mimicry; D015394:Molecular Structure; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D020319:Oligodeoxyribonucleotides, Antisense; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D002945:Cisplatin