Ceramide synthase inhibitor fumonisin B1 inhibits apoptotic cell death in SCC17B human head and neck squamous carcinoma cells after Pc4 photosensitization.

Abstract

The sphingolipid ceramide modulates stress-induced cell death and apoptosis. We have shown that ceramide generated via de novo sphingolipid biosynthesis is required to initiate apoptosis after photodynamic therapy (PDT). The objective of this study was to define the role of ceramide synthase (CERS) in PDT-induced cell death and apoptosis using fumonisin B1 (FB), a CERS inhibitor. We used the silicon phthalocyanine Pc4 for PDT, and SCC17B cells, as a clinically-relevant model of human head and neck squamous carcinoma. zVAD-fmk, a pan-caspase inhibitor, as well as FB, protected cells from death after PDT. In contrast, ABT199, an inhibitor of the anti-apoptotic protein Bcl2, enhanced cell killing after PDT. PDT-induced accumulation of ceramide in the endoplasmic reticulum and mitochondria was inhibited by FB. PDT-induced Bax translocation to the mitochondria and cytochrome c release were also inhibited by FB. These novel data suggest that PDT-induced cell death via apoptosis is CERS/ceramide-dependent.

• Authors: Nithin B Boppana, Mohamed Kodiha, Ursula Stochaj, Ho-sheng Lin, Adriana Haimovitz-Friedman, Alicja Bielawska, Jacek Bielawski, George W Divine, John A Boyd, Mladen Korbelik, Duska Separovic
• Journal: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (Photochem Photobiol Sci) Vol. 13 Issue 11 Pg. 1621-7 (Nov 2014) ISSN: 1474-9092 [Electronic] England
• PMID: 25266739 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Ceramides
• Enzyme Inhibitors
• Fumonisins
• Indoles
• Organosilicon Compounds
• bcl-2-Associated X Protein
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• silicon phthalocyanine
• fumonisin B1
• Cytochromes c
• Oxidoreductases
• dihydroceramide desaturase

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Ceramides (analysis, metabolism)
• Cytochromes c (metabolism)
• Endoplasmic Reticulum (chemistry, metabolism)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Fumonisins (pharmacology, therapeutic use)
• Head and Neck Neoplasms (drug therapy, metabolism, pathology)
• Humans
• Indoles (chemistry)
• Mass Spectrometry
• Mitochondria (chemistry, metabolism)
• Organosilicon Compounds (chemistry)
• Oxidoreductases (antagonists & inhibitors, metabolism)
• Photochemotherapy
• bcl-2-Associated X Protein (metabolism)