Boppana Nithin B, Stochaj Ursula, Kodiha Mohamed, Bielawska Alicja, Bielawski Jacek, Pierce Jason S, Korbelik Mladen, Separovic Duska
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA.
Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1YC, Canada.
J Photochem Photobiol B. 2015 Feb;143:163-8. doi: 10.1016/j.jphotobiol.2015.01.001. Epub 2015 Jan 10.
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.
将光动力疗法（PDT）与另一种抗癌治疗方式相结合是提高疗效的重要策略。将含有硅酞菁光敏剂Pc4的光动力疗法与C6-吡啶鎓神经酰胺（LCL29）相结合，以确定它们促进SCC17B人头颈部鳞状细胞癌细胞死亡的潜力。泛半胱天冬酶抑制剂zVAD-fmk和神经酰胺合酶抑制剂伏马菌素B1（FB）抑制了PDT+LCL29诱导的增强的细胞死亡。定量共聚焦显微镜显示，将PDT与LCL29相结合可增强线粒体中对FB敏感的神经酰胺积累。此外，PDT+LCL29诱导了细胞色素c对FB敏感的重新分布和半胱天冬酶-3的激活增强。总体而言，数据表明PDT+LCL29通过对FB敏感的线粒体神经酰胺积累和细胞凋亡增强了细胞死亡。
