Niccola Funel
University of Pisa, Italy
Title: Different uptake of Ukraine can explain the selective effect against pancreatic adenocarcinoma cell cultures in vitro
Biography
Biography: Niccola Funel
Abstract
Introduction: Current therapy for PDAC is surgery followed by adjuvant chemotherapy for early-stage and palliative chemotherapy for advanced disease. Gemcitabine is the standard drug in both adjuvant and palliative treatment. The mixture of Alkaloids (NSC-631570) in combination with gemcitabine significantly increased the median survival of advanced PDAC patients with respect to gemcitabine alone (10.4 vs. 5.2 months; p<0.001). Furthermore, preclinical studies showed that this mixture had selective citotoxic effects in cancer cell lines derived from different tumor types, but not in normal cell lines.
Aim: To evaluate the citotoxic effects of NSC-631570 in 2 Primary Pancreatic Cancer Cell Lines (PPTCCs), fibroblasts derived from PDAC specimens (F-PDAC) and an immortalized epithelial ductal pancreatic cell line (HNPE).
Materials & methods: Cytotoxicity was assessed by the CellTiter 96 kit (Promega) based on the cellular metabolism of the tetrazolium compound XTT, which is reduced by living cells to yield a soluble formazan product in the presence of the electron coupling agent phenazine methosulfate, while the modulation of Ukrain uptake in the medium was studied using the fluorescence property of NSC-631570 with the AlphaDigiDoc software by UV light excitation (ULA-DC test).
Results: Citotoxic effects of Ukrain in PPTCCs were significantly higher than those observed in F-PDAC and HPNE cells (20% vs. 80% live cells, at 10 µM [drug]). Furthermore, the ULA-DC test revealed that PPTCCs cells consumed more drug than F-PDAC and HPNE cells (paired Student’s test, n=4, p<0.001).
Conclusion: These data demonstrated the selective effect of NSC-631570 in PPTCCs, which may be related to a different transport system or higher metabolism of the drug in PDAC. Indeed, the two different up-takes of alkaloids discovered in cancer and no pancreatic cancer cells seem to suggest a higher expression of multi drug resistant systems (MDR) in F-PDAC and HPNE cells and warrant further investigations in order to support the possible role of Ukraine in PDAC treatment.