Abstract | BACKGROUND: METHODS: RESULTS: Stimulation of tumor-derived cells with the different inhibitors tested revealed a complex pattern, whereby proliferation inhibiting and survival reducing concentrations varied in [18F]-fluoro- deoxyglucose uptake experiments more than one order of magnitude among the different cells tested. We found that the effects of GMX1778 and STF-31 could be partially abolished by (i) nicotinic acid (NA) only in nicotinic acid phosphoribosyltransferase (NAPRT) expressing cells and (ii) nicotinamide mononucleotide (NMN) in all cells tested, supporting the classification of these compounds as NAMPT inhibitors. In short-time [18F]-fluoro- deoxyglucose uptake experiments the application of WZB-117 was found to lead to an almost complete uptake inhibition in all cells tested, whereas the effect of fasentin was found to be cell type dependent with a maximum value of ~35% in A172, BHY, HeLa and HT-29 cells. We also found that STF-31 inhibited glucose uptake in all cells tested in a range of 25-50%. These data support the classification of STF-31 as a GLUT inhibitor. CONCLUSIONS: Our data reveal a dual mode of action of STF-31, serving either as a NAMPT or as a GLUT inhibitor, whereby the latter seems to be apparent only at higher STF-31 concentrations. The molecular basis of such a dual function and its appearance in compounds previously designated as NAMPT-specific inhibitors requires further investigation.
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Authors | Dominik Kraus, Jan Reckenbeil, Nadine Veit, Stefan Kuerpig, Michael Meisenheimer, Imke Beier, Helmut Stark, Jochen Winter, Rainer Probstmeier |
Journal | Cellular oncology (Dordrecht)
(Cell Oncol (Dordr))
Vol. 41
Issue 5
Pg. 485-494
(Oct 2018)
ISSN: 2211-3436 [Electronic] Netherlands |
PMID | 29949049
(Publication Type: Journal Article)
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Chemical References |
- Anilides
- Glucose Transport Proteins, Facilitative
- Hydroxybenzoates
- Pyridines
- STF-31
- WZB117
- fasentin
- NAD
- Nicotinamide Phosphoribosyltransferase
- Glucose
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Topics |
- Anilides
(pharmacology)
- Biological Transport
(drug effects)
- Blotting, Western
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Glucose
(metabolism)
- Glucose Transport Proteins, Facilitative
(antagonists & inhibitors, metabolism)
- Humans
- Hydroxybenzoates
(pharmacology)
- NAD
(metabolism)
- Nicotinamide Phosphoribosyltransferase
(metabolism)
- Pyridines
(pharmacology)
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