C6-pyridinium ceramide sensitizes SCC17B human head and neck squamous cell carcinoma cells to photodynamic therapy.

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.

• Authors: Nithin B Boppana, Ursula Stochaj, Mohamed Kodiha, Alicja Bielawska, Jacek Bielawski, Jason S Pierce, Mladen Korbelik, Duska Separovic
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 143 Pg. 163-8 (Feb 2015) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 25635908 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• 2-N-(6'-(1''-pyridinium)hexanoyl)sphingosine
• Amino Acid Chloromethyl Ketones
• Ceramides
• Fumonisins
• Indoles
• Organosilicon Compounds
• Photosensitizing Agents
• Pyridinium Compounds
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• silicon phthalocyanine
• fumonisin B1
• Cytochromes c
• Caspase 3

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (drug effects, radiation effects)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Ceramides (pharmacology)
• Cytochromes c (metabolism)
• Drug Synergism
• Enzyme Activation (drug effects, radiation effects)
• Fumonisins (pharmacology)
• Head and Neck Neoplasms (drug therapy, pathology)
• Humans
• Indoles (pharmacology)
• Mitochondria (drug effects, metabolism, radiation effects)
• Organosilicon Compounds (pharmacology)
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• Protein Transport (drug effects, radiation effects)
• Pyridinium Compounds (pharmacology)