Fig. 5: CPX targets the Notch signaling pathway, through inhibition of the γ-secretase complex. | Cell Death & Disease

Fig. 5: CPX targets the Notch signaling pathway, through inhibition of the γ-secretase complex.

From: Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Fig. 5: CPX targets the Notch signaling pathway, through inhibition of the γ-secretase complex.The alternative text for this image may have been generated using AI.

A CPX inhibits mRNA expression of genes involved in Wnt, Hedgehog, and Notch cell signaling pathways. RNA extracted from T24 cells treated with and without CPX for 48 h was used to generate cDNA. The samples were analyzed using a Human stem cell RT2 profiler PCR array to identify signaling pathways that important for stem cell maintenance like Notch signaling and Wnt signaling. Expression of Hes5, Lfng, Myc, and Notch 1 mRNAs were significantly downregulated after CPX treatment. B CPX affects the expression of Notch receptors. Western blot analysis demonstrates that CPX treatment increased the expression of Notch 1 and suppressed the activation of Notch 2 and Notch 3, while CPX has little to no effect on Notch 4. C CPX suppresses γ-secretase pathway proteins. Western blot analysis of CPX-treated T24 and UM-UC-3 cell lysates showed CPX treatment reduced levels of Nicastrin, Presenilin 1, APH-1, and PEN-2. D CPX suppresses notch signaling pathway ligand and downstream proteins. CPX increased the expression of ligand Jagged 1 and inhibited the expression of downstream targets Hes1, cMYC, and Cyclin D1 in T24 and UM-UC-3 cells.

Back to article page