Abstract
We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4 + ) can act as photosensitizers with efficacy comparable to that of hematoporphyrin derivative (HpD) in preventing cell proliferation and causing cell death in vitro. To better understand the biochemical basis of this activity, the effects of photo-activated ZnTM-3-PyP4 + on GSH/GSSG ratio, lipid peroxidation, membrane permeability, oxidative DNA damage, and the activities of SOD, catalase, glutathione reductase, and glutathione peroxidase were evaluated. Light exposure of ZnTM-3-PyP4 + -treated colon adenocarcinoma cells caused a wide spectrum of oxidative damage including depletion of GSH, inactivation of glutathione reductase and glutathione peroxidase, oxidative DNA damage and peroxidation of membrane lipids. Cell staining with Hoechst-33342 showed morphological changes consistent with both necrotic and apoptotic death sequences, depending upon the presence of oxygen.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalase / drug effects
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Catalase / metabolism
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Cell Line, Tumor
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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DNA Damage / drug effects
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DNA Damage / physiology
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Glutathione / drug effects
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Glutathione / metabolism
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Glutathione Disulfide / drug effects
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Glutathione Disulfide / metabolism
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Glutathione Peroxidase / drug effects
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Glutathione Peroxidase / metabolism
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Glutathione Reductase / drug effects
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Glutathione Reductase / metabolism
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Humans
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / physiology
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Metalloporphyrins / toxicity*
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Oxidative Stress / drug effects*
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Oxidative Stress / physiology
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Photosensitivity Disorders
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Photosensitizing Agents / toxicity*
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Superoxide Dismutase / drug effects
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Superoxide Dismutase / metabolism
Substances
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Metalloporphyrins
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Photosensitizing Agents
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zinc hematoporphyrin
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Catalase
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Glutathione Peroxidase
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Superoxide Dismutase
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Glutathione Reductase
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Glutathione
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Glutathione Disulfide