title: 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: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA.
authors: Nithin B
authors: NB
authors: Boppana
authors: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1YC, Canada.
authors: Ursula
authors: U
authors: Stochaj
authors: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1YC, Canada.
authors: Mohamed
authors: M
authors: Kodiha
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA.
authors: Alicja
authors: A
authors: Bielawska
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA.
authors: Jacek
authors: J
authors: Bielawski
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC 29425, USA.
authors: Jason S
authors: JS
authors: Pierce
authors: British Columbia Cancer Agency, 675 West 10th Ave., Vancouver, BC V5Z 1L3, Canada.
authors: Mladen
authors: M
authors: Korbelik
authors: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA; Karmanos Cancer Institute, Wayne State University, 4100 John R, Detroit, MI 48201, USA. Electronic address: dseparovic@wayne.edu.
authors: Duska
authors: D
authors: Separovic
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D037341:Fumonisins / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017646:Organosilicon Compounds / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011726:Pyridinium Compounds / Q000494:pharmacology*
chemical_list: C539200:2-N-(6'-(1''-pyridinium)hexanoyl)sphingosine; D000590:Amino Acid Chloromethyl Ketones; D002518:Ceramides; D037341:Fumonisins; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D011726:Pyridinium Compounds; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C082854:silicon phthalocyanine; C056933:fumonisin B1; D045304:Cytochromes c; D053148:Caspase 3
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