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3PO as a Selective Inhibitor of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 in A375 Human Melanoma Cells.

Anticancer research (2020-05-06)
Krzysztof Kotowski, Stanisław Supplitt, Daniel Wiczew, Dawid Przystupski, Weronika Bartosik, Jolanta Saczko, Joanna Rossowska, Małgorzata Drąg-Zalesińska, Olga Michel, Julita Kulbacka
RÉSUMÉ

The occurrence of BRAFV600E mutation causes an up-regulation of the B-raf kinase activity leading to the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α) - the promoter of the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) enzyme. The aim of the study was to examine the effect of the (2E)-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), as an inhibitor of PFKFB3, on human melanoma cells (A375) with endogenous BRAFV600E mutation. A375 cells were exposed to different concentrations of 3PO and the following tests were performed: docking, cytotoxicity assay, immunocytochemistry staining glucose uptake, clonogenic assay, holotomography imaging, and flow cytometry. Our studies revealed that 3PO presents a dose-dependent and time-independent cytotoxic effect and promotes apoptosis of A375 cells. Furthermore, the obtained data indicate that 3PO induces cell cycle arrest in G1/0 and glucose uptake reduction. Taking all together, our research demonstrated a here should be proapoptotic and antiproliferative effect of 3PO on A375 human melanoma cells.

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Sigma-Aldrich
Diméthylsulfoxyde, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Iodure de propidium, ≥94% (HPLC)
Seringues SGE pour passeur d′échantillon Agilent/HP 7673 et 7683 et 6850 ALS, aiguille soudée, volume 10 μL, SK-10F-HP-0.63, needle size 23 ga, needle L 42 mm, pkg of 6 ea
Sigma-Aldrich
3PO, ≥98% (HPLC)
Sigma-Aldrich
p-Xylene-bis(N-pyridinium bromide), ≥95% (TLC)