Session Speaker

Omeprazole Inhibits Proliferation and Induces Autophagy in Pancreatic Cancer Cells
Andrej Udelnow, Andreas Kreyes, Katharina Landfester, Paul Walther, Thomas Klapperstueck, Johannes Wohlrab, Doris Henne-Bruns, Uwe Knippschild, Peter Wuerl
Germany

Omeprazole (OMP) has been recently described as a modulator of tumor chemoresistance and since pancreatic tumors are highly chemoresistant a logical step would be to investigate the effects of omeprazole on pancreatic cancer cell lines (MiaPaCa-2 and ASPC-1).

Dose effect-curves of OMP and 5-fluorouracile (5-FU) were generated. In addition, transmission electron microscopy (TEM) and proton nuclear magnetic resonance (NMR) spectroscopy were performed. Furthermore, gene expression of the apoptosis-related bad gene as well as of mdr-1 and the vacuolar H+/K+-ATPase was analysed under 5-FU and OMP. Moreover, the expression of ATG12 in cells as well as of LAMP-1, Cathepsine-D and β-COP in lysosome and Golgi complex containing cell fractions were investigated by Western Blots.

The dose-effect-curves revealed that omeprazole inhibits proliferation of pancreatic cancer cells in non-toxic concentrations, which is accounted for by autophagy induction as shown by TEM, NMR and ATG12-induction. In addition for the first time, in MiaPaCa-2 cells, OMP was observed intracellularly by NMR spectroscopy.

The autophagic death induced by omeprazole may circumvent common resistance mechanisms of pancreatic cancer. Since omeprazole use has already been established in clinical practice; these results could rapidly lead to the development of new therapeutic concepts.