Journal article
Increased efficacy of in vitro Photofrin ® photosensitization of human oral squamous cell carcinoma by iron and ascorbate
Journal of photochemistry and photobiology. B, Biology, Vol.40(3), pp.273-277
1997
DOI: 10.1016/S1011-1344(97)00068-7
PMID: 9372616
Abstract
Photofrin
®, a photosensitizer used in the photodynamic therapy of cancer, selectively localizes in cellular membranes. Upon exposure to visible light, Photofrin
® produces singlet oxygen (
1O
2), which reacts with membrane polyunsaturated fatty acids forming lipid hydroperoxides. Transition metals, such as Fe
2+, catalyze the production of cytotoxic free radicals from lipid hydroperoxides. Ascorbate reduces ferric to ferrous iron, further augmenting lipid peroxidation. Therefore, to increase the efficacy of Photofrin
® photosensitization, we added 20 μM ferrous sulfate and 100 μM ascorbic acid, in an aqueous layer over SCC-25 oral squamous cell carcinoma cells during
in vitro illumination. In electron paramagnetic resonance spin trapping experiments, using POBN (α-(4-pyridyl-1-oxide)-
N-tert-butylnitrone), we observed that the presence of this pro-oxidant combination greatly increases the production of membrane-derived lipid free radicals. The effect was time dependent but only partially concentration dependent. Trypan blue dye exclusion demonstrated that this increase in lipid radical formation correlated with cytotoxicity. These observations support the hypothesis that Photofrin
® photosensitization leads to lipid hydroperoxide formation, which increases the cell's susceptibility to iron-induced Fenton chemistry. The resulting free radical-mediated lipid peroxidation results in cell death. From these data we hypothesize that the efficacy of photodynamic therapy of superficial cancer might be increased by the topical application of the pro-oxidant combination of iron and ascorbate. Furthermore, their use will probably allow lower doses of Photofrin
® without compromising antitumor effect.
Details
- Title: Subtitle
- Increased efficacy of in vitro Photofrin ® photosensitization of human oral squamous cell carcinoma by iron and ascorbate
- Creators
- Eric E Kelley - The University of Iowa College of Medicine, Department of Internal Medicine, Iowa City, IA 52242, USAFrederick E Domann - Radiation Research Laboratory, Department of Radiology, The University of Iowa, Iowa City, IA 52242, USAGarry R Buettner - The University of Iowa, Free Radical Research Institute, Iowa City, IA 52242, USALarry W Oberley - Radiation Research Laboratory, Department of Radiology, The University of Iowa, Iowa City, IA 52242, USAC.Patrick Burns - The University of Iowa College of Medicine, Department of Internal Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Journal of photochemistry and photobiology. B, Biology, Vol.40(3), pp.273-277
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S1011-1344(97)00068-7
- PMID
- 9372616
- ISSN
- 1011-1344
- eISSN
- 1873-2682
- Language
- English
- Date published
- 1997
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984047701802771
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