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ω-3 and ω-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme

1
Department of Pharmacology and Toxicology, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
2
Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada
3
Center for Aging and Associated Diseases, Zewail City of Science and Technology, Giza 12578, Egypt
*
Authors to whom correspondence should be addressed.
Nutrients 2018, 10(4), 454; https://doi.org/10.3390/nu10040454
Received: 22 February 2018 / Revised: 26 March 2018 / Accepted: 3 April 2018 / Published: 6 April 2018
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Abstract

Glioblastoma multiforme (GBM) is a highly infiltrative brain cancer with a dismal prognosis. High levels of brain fatty acid binding protein (B-FABP) are associated with increased migration/infiltration in GBM cells, with a high ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) driving B-FABP-mediated migration. Since several protein kinase Cs (PKCs) are overexpressed in GBM and linked to migration, we explored a possible relationship between B-FABP and levels/activity of different PKCs, as a function of AA and DHA supplementation. We report that ectopic expression of B-FABP in U87 cells alters the levels of several PKCs, particularly PKCζ. Upon analysis of PKCζ RNA levels in a panel of GBM cell lines and patient-derived GBM neurospheres, we observed a trend towards moderate positive correlation (r = 0.624, p = 0.054) between B-FABP and PKCζ RNA levels. Analysis of PKC activity in U87 GBM cells revealed decreased typical PKC activity (23.4%) in B-FABP-expressing cells compared with nonexpressing cells, with no difference in novel and atypical PKC activities. AA and DHA modulated both conventional and atypical PKC activities in a B-FABP-dependent manner, but had no effect on novel PKC activity. These results suggest that conventional and atypical PKCs are potential downstream effectors of B-FABP/fatty acid-mediated alterations in GBM growth properties. View Full-Text
Keywords: Glioblastoma multiforme; brain fatty acid binding protein; protein kinase C; docosahexaenoic acid; arachidonic acid Glioblastoma multiforme; brain fatty acid binding protein; protein kinase C; docosahexaenoic acid; arachidonic acid
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Elsherbiny, M.E.; Chen, H.; Emara, M.; Godbout, R. ω-3 and ω-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in Glioblastoma Multiforme. Nutrients 2018, 10, 454.

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