Abstract
Combining photodynamic therapy (PDT) with another anticancer treatment modality is an important strategy for improved efficacy. PDT with Pc4, a silicon phthalocyanine photosensitizer, was combined with C6-pyridinium ceramide (LCL29) to determine their potential to promote death of SCC17B human head and neck squamous cell carcinoma cells. PDT+LCL29-induced enhanced cell death was inhibited by zVAD-fmk, a pan-caspase inhibitor, and fumonisin B1 (FB), a ceramide synthase inhibitor. Quantitative confocal microscopy showed that combining PDT with LCL29 enhanced FB-sensitive ceramide accumulation in the mitochondria. Furthermore, PDT+LCL29 induced enhanced FB-sensitive redistribution of cytochrome c and caspase-3 activation. Overall, the data indicate that PDT+LCL29 enhanced cell death via FB-sensitive, mitochondrial ceramide accumulation and apoptosis.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Apoptosis / drug effects
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Apoptosis / radiation effects
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Carcinoma, Squamous Cell / drug therapy*
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Carcinoma, Squamous Cell / pathology*
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Caspase 3 / metabolism
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Cell Line, Tumor
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Ceramides / pharmacology*
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Cytochromes c / metabolism
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Drug Synergism
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Enzyme Activation / drug effects
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Enzyme Activation / radiation effects
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Fumonisins / pharmacology
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Head and Neck Neoplasms / drug therapy*
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Head and Neck Neoplasms / pathology*
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Humans
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Indoles / pharmacology*
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / radiation effects
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Organosilicon Compounds / pharmacology*
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Photochemotherapy*
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Photosensitizing Agents / pharmacology*
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Protein Transport / drug effects
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Protein Transport / radiation effects
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Pyridinium Compounds / pharmacology*
Substances
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2-N-(6'-(1''-pyridinium)hexanoyl)sphingosine
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Amino Acid Chloromethyl Ketones
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Ceramides
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Fumonisins
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Indoles
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Organosilicon Compounds
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Photosensitizing Agents
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Pyridinium Compounds
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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silicon phthalocyanine
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fumonisin B1
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Cytochromes c
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Caspase 3