| Popis: |
The failure of current chemotherapeutic agents for pancreatic cancer (PCa) makes it the most aggressive soft tissue tumor with a 5-year survival of slightly above 10% and is estimated to be the second leading cause of cancer death by 2030. Objective: The main aim was to synthesize, characterize and evaluate the in-vitro anticancer activity of 1,3-bistetrahydrofuran-2yl-5FU (MFU). Methods: MFU was synthesized by using 5-fluorouracil (5-FU) and tetrahydrofuran acetate, and characterized by nuclear magnetic resonance (NMR), micro-elemental analysis, high-performance liquid chromatography (HPLC), and liquid chromatography with mass spectrophotometry (LC-MS). MFU and Gemcitabine hydrochloride (GemHCl) were tested for antiproliferative activity against MiaPaca-2 and Panc-1 cell lines. Results: The half-minimum inhibitory concentration (IC50) of MFU was twice lower than that of GemHCl when used in both cell lines. MiaPaca-2 cells (MFU-IC50 =4.5±1.2μM vs. GemHCl-IC50=10.3±1.1μM); meanwhile similar trend was observed in Panc-1 cells (MFU-IC50=3.0 ±1μM vs. GemHCl-IC50=6.1±1.03μM). The MFU and GemHCl effects on 3D spheroids showed a similar trend (IC50-GemHCl=14.3±1.1μM vs. IC50-MFU =7.2±1.1μM) for MiaPaca-2 cells, and (IC50-GemHCl=16.3±1.1μM vs. IC50-MFU=9.2±1.1μM) for Panc-1 cells. MFU significantly inhibited clonogenic cell growth, and induced cell death via apoptosis. Cell cycle data showed mean PI for GemHCl (48.5 - 55.7) twice higher than MFU (24.7 to 27.9) for MiaPaca-2 cells, and similarly to Panc-1 cells. The in-vivo model showed intensely stained EGFR (stained brown) in all mice tumors, however, HER2 expression was less stained in MFU-treated tumors compared to GemHCl-treated tumors and controls. Conclusion: MFU was synthesized with high purity and may have potential anticancer activity against Pca. |
