Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options

SIMPLE SUMMARY: Compounds interfering with glucose uptake and NAD metabolism are potential candidates for cancer therapy. Tumor cells are sensitive to such compounds in terms of glucose uptake as well as cell proliferation and survival. We have carried out these types of studies to neuroendocrine tumor (NET) cells, i.e., pancreatic Bon-1 and QPG-1 NET cell lines and GLC-2 and GLC-36 small cell lung cancer (SCLC) cell lines. Cells treated with substances that provoke a chemical inhibition of facilitative glucose transporters (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD metabolism, lead to decreased cell proliferation and increased cell death. ABSTRACT: (1) Background: the potency of drugs that interfere with glucose metabolism, i.e., glucose transporters (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT) was analyzed in neuroendocrine tumor (NET, BON-1, and QPG-1 cells) and small cell lung cancer (SCLC, GLC-2, and GLC-36 cells) tumor cell lines. (2) Methods: the proliferation and survival rate of tumor cells was significantly affected by the GLUT-inhibitors fasentin and WZB1127, as well as by the NAMPT inhibitors GMX1778 and STF-31. (3) Results: none of the NET cell lines that were treated with NAMPT inhibitors could be rescued with nicotinic acid (usage of the Preiss–Handler salvage pathway), although NAPRT expression could be detected in two NET cell lines. We finally analyzed the specificity of GMX1778 and STF-31 in NET cells in glucose uptake experiments. As previously shown for STF-31 in a panel NET-excluding tumor cell lines, both drugs specifically inhibited glucose uptake at higher (50 μM), but not at lower (5 μM) concentrations. (4) Conclusions: our data suggest that GLUT and especially NAMPT inhibitors are potential candidates for the treatment of NET tumors.