Fenofibrate: an established drug used for dyslipidemia displays anti-cancer potential in a 3D co-culture model

Abstract (as presented by the authors of the scientific work):

"Lymph node metastasis of breast cancer is a clinical marker of poor prognosis. Yet, there exist no therapies targeting mechanisms of intravasation into lymphatics. Herein we report on an effect of the antidyslipidemic drug fenofibrate with vasoprotective activity, which attenuates breast cancer intravasation in vitro, and describe the potential mechanisms. To measure intravasation in a 3-dimensional co-culture model MDA-MB231 and MCF-7 breast cancer spheroids were placed on immortalised lymphendothelial cell (LEC) monolayers. This provokes the formation of circular chemorepellent induced defects (CCIDs) in the LEC barrier resembling entry ports for the intravasating tumour. Furthermore, the expression of adhesion molecules ICAM-1, CD31 and FAK was investigated in LECs by western blotting as well as cell-cell adhesion and NF-κB activity by respective assays. In MDA-MB231 cells the activity of CYP1A1 was measured by EROD assay. Fenofibrate inhibited CCID formation in the MDA-MB231/LEC- and MCF-7/LEC models and the activity of NF-κB, which in turn downregulated ICAM-1 in LECs and the adhesion of cancer cells to LECs. Furthermore, CD31 and the activity of FAK were inhibited. In MDA-MB231 cells, fenofibrate attenuated CYP1A1 activity. Combinations with other FDA-approved drugs, which reportedly inhibit different ion channels, attenuated CCID formation additively or synergistically. In summary, fenofibrate inhibited NF-κB and ICAM-1, and inactivated FAK, thereby attenuating tumour intravasation in vitro. A combination with other FDA-approved drugs further improved this effect. Our new concept may lead to a novel therapy for cancer patients."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):

Access to the referenced scientific work (PDFs could be provided by the authors):

Nguyen CH, Huttary N, Atanasov AG, Chatuphonprasert W, Brenner S, Fristiohady
A, Hong J, Stadler S, Holzner S, Milovanovic D, Dirsch VM, Kopp B, Saiko P, Krenn
L, Jäger W, Krupitza G. Fenofibrate inhibits tumour intravasation by several
independent mechanisms in a 3-dimensional co-culture model. Int J Oncol. 2017
May;50(5):1879-1888. doi: 10.3892/ijo.2017.3956. Epub 2017 Apr 7. PubMed PMID:
28393180.
https://www.researchgate.net/publication/315929103_Fenofibrate_inhibits_tumour_intravasation_by_several_independent_mechanisms_in_a_3-dimensional_co-culture_model
...or...
https://www.spandidos-publications.com/10.3892/ijo.2017.3956


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