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Fumonisin B1 Inhibits Endoplasmic Reticulum Stress Associated-apoptosis After FoscanPDT Combined with C6-Pyridinium Ceramide or Fenretinide.
- Source :
-
Anticancer research [Anticancer Res] 2017 Feb; Vol. 37 (2), pp. 455-463. - Publication Year :
- 2017
-
Abstract
- Background/aim: Combining an anticancer agent fenretinide (HPR) or C6-pyridinium ceramide (LCL29) with Foscan-mediated photodynamic therapy (FoscanPDT) is expected to augment anticancer benefits of each substance. We showed that treatment with FoscanPDT+HPR enhanced accumulation of C16-dihydroceramide, and that fumonisin B1 (FB), an inhibitor of ceramide synthase, counteracted caspase-3 activation and colony-forming ability of head and neck squamous cell carcinoma (HNSCC) cells. Because cancer cells appear to be more susceptible to increased levels of the endoplasmic reticulum (ER) stress than normal cells, herein we tested the hypothesis that FoscanPDT combined with HPR or LCL29 induces FB-sensitive ER stress-associated apoptosis that affects cell survival.<br />Materials and Methods: Using an HNSCC cell line, we determined: cell survival by clonogenic assay, caspase-3 activity by spectrofluorometry, the expression of the ER markers BiP and CHOP by quantitative real-time polymerase chain reaction and western immunoblotting, and sphingolipid levels by mass spectrometry.<br />Results: Similar to HPR+FoscanPDT, LCL29+FoscanPDT induced enhanced loss of clonogenicity and caspase-3 activation, that were both inhibited by FB. Our additional pharmacological evidence showed that the enhanced loss of clonogenicity after the combined treatments was singlet oxygen-, ER stress- and apoptosis-dependent. The combined treatments induced enhanced, FB-sensitive, up-regulation of BiP and CHOP, as well as enhanced accumulation of sphingolipids.<br />Conclusion: Our data suggest that enhanced clonogenic cell killing after the combined treatments is dependent on oxidative- and ER-stress, apoptosis, and FB-sensitive sphingolipid production, and should help develop more effective mechanism-based therapeutic strategies.<br /> (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Subjects :
- Apoptosis drug effects
Carcinoma, Squamous Cell metabolism
Carcinoma, Squamous Cell pathology
Caspase 3 metabolism
Caspase Inhibitors pharmacology
Cell Line, Tumor
Combined Modality Therapy
Head and Neck Neoplasms metabolism
Head and Neck Neoplasms pathology
Humans
Radiation-Sensitizing Agents pharmacology
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell drug therapy
Ceramides pharmacology
Endoplasmic Reticulum Stress drug effects
Fenretinide pharmacology
Fumonisins pharmacology
Head and Neck Neoplasms drug therapy
Mesoporphyrins pharmacology
Photochemotherapy methods
Pyridinium Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 37
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 28179290
- Full Text :
- https://doi.org/10.21873/anticanres.11337