当前位置： SCI文献检索 > JOURNAL OF INORGANIC BIOCHEMISTRY期刊下所有文献 > Cell death by reactive oxygen species generated from water-soluble cationic metalloporphyrins as superoxide dismutase mimics.

Cell death by reactive oxygen species generated from water-soluble cationic metalloporphyrins as superoxide dismutase mimics.

Abstract：

:We investigated the effect on cell death of reactive oxygen species induced by water-soluble cationic metalloporphyrins with superoxide dismutase (SOD) activity. The SOD activity of 5,10,15,20-tetrakis(4-N-methylpyridyl)]porphine (MPy(4)P) containing Fe, Mn or Cu was measured using a cytochrome c assay by the xanthine/xanthine oxidase system and stopped-flow kinetic analysis. Cell viability of four cell lines treated with metalloporphyrins, mitomycin c (MMC), or cisplatin was estimated by a trypan blue exclusion assay. FeMPy(4)P with a high SOD activity showed a significant cytotoxicity compared with MMC and cisplatin, while CuMPy(4)P without SOD activity exhibited no cytotoxicity. However, MnMPy(4)P showing an SOD activity as high as that of FeMPy(4)P did not indicate cytotoxicity. These findings suggest that FeMPy(4)P as SOD mimic converts intracellular O2(*-) to H(2)O(2) and that it rapidly reacts with H(2)O(2) to form *OH, causing DNA damage and inducing cell death. On the other hand, MnMPy(4)P did not participate in the Fenton reaction, so that DNA damage in the cells treated with MnMPy(4)P was not observed. In addition, the cytotoxicity by the metalloporphyrin was inversely correlated with the SOD activity of the cells and the selective damage at cellular and DNA levels was confirmed. We believe that for an anticancer drug with antioxidant ability O(2)(*-) is useful as a target molecule to induce selective cell death between cancer and normal cells and that metalloporphyrins showing SOD activity and Fenton-like reaction are a new class of anticancer agents.

journal_name

J Inorg Biochem

journal_title

Journal of inorganic biochemistry

authors

Ohse T,Nagaoka S,Arakawa Y,Kawakami H,Nakamura K

doi

10.1016/s0162-0134(01)00187-8

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

201-8

issue

2-3

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(01)00187-8

journal_volume

85

pub_type

杂志文章

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