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

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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 photo-dynamic 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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48201, USA

    Nithin B. Boppana, John A. Boyd & Duska Separovic

  2. Department of Physiology, McGill University, Montreal, QC, H3G 1YC, Canada

    Mohamed Kodiha & Ursula Stochaj

  3. Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Wayne State University, Detroit, MI, 48201, USA

    Ho-sheng Lin

  4. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Adriana Haimovitz-Friedman

  5. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA

    Alicja Bielawska & Jacek Bielawski

  6. Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, 48202, USA

    George W. Divine

  7. British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada

    Mladen Korbelik

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  1. Nithin B. Boppana
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  2. Mohamed Kodiha
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Correspondence to Duska Separovic.

Additional information

Electronic supplementary information (ESI) available. See DOI: 10.1039/c4pp00292j

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Boppana, N.B., Kodiha, M., Stochaj, U. et al. Ceramide synthase inhibitor fumonisin B1 inhibits apoptotic cell death in SCC17B human head and neck squamous carcinoma cells after Pc4 photosensitization. Photochem Photobiol Sci 13, 1621–1627 (2014). https://doi.org/10.1039/c4pp00292j

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  • DOI: https://doi.org/10.1039/c4pp00292j

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