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

  • 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.

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Document Type:Article
Author:Jochen Winter, Rudolf Kunze, Nadine Veit, Stefan Kuerpig, Michael Meisenheimer, Dominik Kraus, Alexander Glassmann, Rainer Probstmeier
Parent Title (English):Cancers
Article Number:1415
Number of pages:11
Place of publication:Basel
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2023/02/23
Copyright:© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
Funding:This research received no external funding.
Keyword:GMX1778; STF-31; WZB117; fasentin; glucose uptake inhibitor; neuroendocrine
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2023/03/07
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International