Cytotoxic effects of Mn(III) N-alkylpyridylporphyrins in the presence of cellular reductant, ascorbate

Document Type

Article

Abstract

Due to the ability to easily accept and donate electrons Mn(III)N-alkylpyridylporphyrins (MnPs) can dismute O 2·-, reduce peroxynitrite, but also generate reactive species and behave as pro-oxidants if conditions favour such action. Herein two ortho isomers, MnTE-2-PyP 5+, MnTnHex-2-PyP 5+, and a meta isomer MnTnHex-3-PyP 5+, which differ greatly with regard to their metal-centered reduction potential, E 1/2 (Mn IIIP/Mn IIP) and lipophilicity, were explored. Employing Mn IIIP/Mn IIP redox system for coupling with ascorbate, these MnPs catalyze ascorbate oxidation and thus peroxide production. Consequently, cancer oxidative burden may be enhanced, which in turn would suppress its growth. Cytotoxic effects on Caco-2, Hela, 4T1, HCT116 and SUM149 were studied. When combined with ascorbate, MnPs killed cancer cells via peroxide produced outside of the cell. MnTE-2-PyP 5+ was the most efficacious catalyst for peroxide production, while MnTnHex-3-PyP 5+ is most prone to oxidative degradation with H 2 , and thus the least efficacious. A 4T1 breast cancer mouse study of limited scope and success was conducted. The tumour oxidative stress was enhanced and its microvessel density reduced when mice were treated either with ascorbate or MnP/ascorbate; the trend towards tumour growth suppression was detected. © 2011 Informa UK, Ltd.

Keywords

Ascorbate, Cancer cells, Mn porphyrin, MnTE-2-PyP 5+, Oxidative stress, SOD mimics

Publication Date

11-1-2011

Publication Title

Free Radical Research

ISSN

10715762

E-ISSN

10292470

Volume

45

Issue

11-12

First Page

1289

Last Page

1306

PubMed ID

21859376

Digital Object Identifier (DOI)

10.3109/10715762.2011.616199

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