Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells
Kakkassery, Vinodh and Skosyrski, S. and Lüth, A. and Kleuser, B. and van der Giet, M. and Tate, R. and Reinhard, J. and Faissner, A. and Joachim, S. C. and Kociok, N. (2017) Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells. Pathology & Oncology Research. ISSN 1532-2807 (https://doi.org/10.1007/s12253-017-0360-x)
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Abstract
Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). Only sphingosine-1-P up-regulation was significantly increased in WERI EtoR (p < 0.01), but not in WERI Rb1 (p > 0.2). Both cell lines upregulate pro-apoptotic sphingosine after etoposide incubation, but only WERI EtoR produces additional survival favorable sphingosine-1-P. These data may suggest a role of sphingosine-1-P in retinoblastoma chemotherapy resistance, although this seems not to be the only resistance mechanism.
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Item type: Article ID code: 62927 Dates: DateEvent15 November 2017Published15 November 2017Published Online27 October 2017AcceptedNotes: This is a post-peer-review, pre-copyedit version of an article published in Pathology oncology research. The final authenticated version is available online at: https://doi.org/10.1007/s12253-017-0360-x Subjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 18 Jan 2018 10:35 Last modified: 04 Sep 2024 00:57 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/62927