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

by Selleckchem | Jul 06 2023

(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.

Comments:

(1) The study focused on analyzing the effectiveness of drugs that target glucose metabolism, specifically glucose transporters (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT), in neuroendocrine tumor (NET) and small cell lung cancer (SCLC) cell lines. The specific cell lines used in the study were BON-1 and QPG-1 for NET, and GLC-2 and GLC-36 for SCLC.

(2) The researchers assessed the impact of GLUT inhibitors, such as fasentin and WZB1127, as well as NAMPT inhibitors, including GMX1778 and STF-31, on the proliferation and survival rate of the tumor cells.

(3) The results indicated that the proliferation and survival of tumor cells were significantly affected by the GLUT inhibitors and NAMPT inhibitors. In the case of the NET cell lines treated with NAMPT inhibitors, none of them could be rescued with nicotinic acid, which is involved in the Preiss-Handler salvage pathway. However, NAPRT expression, which is related to nicotinic acid utilization, was detected in two of the NET cell lines. Additionally, the researchers conducted glucose uptake experiments to assess the specificity of GMX1778 and STF-31 in NET cells. Similar to previous findings in other tumor cell lines excluding NET, both drugs specifically inhibited glucose uptake at higher concentrations (50 μM) but not at lower concentrations (5 μM).

(4) Based on these findings, the researchers concluded that GLUT and, particularly, NAMPT inhibitors show promise as potential treatment options for NET tumors.

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