Targeting glucose transport and the NAD pathway in tumor cells with STF-31: a re-evaluation.

摘要: Targeting glucose metabolism is a promising way to interfere with tumor cell proliferation and survival. However, controversy exists about the specificity of some targeting anticancer drugs. Especially potency STF-31 has been debated. Here, we aimed assess impact transporter (GLUT) inhibitors fasentin WZB117, nicotinamide phosphoribosyltransferase (NAMPT) GMX1778 on survival, as well uptake. Tumor-derived A172 (glioblastoma), BHY (oral squamous carcinoma), HeLa (cervix adenocarcinoma), HN (head neck cancer), HT-29 (colon carcinoma) MG-63 (osteosarcoma) cells were treated fasentin, STF-31. Proliferation rates viabilities assessed using XTT, crystal violet LDH assays. mRNA protein expression GLUT1 NAPRT qPCR Western blotting, respectively. The effects inhibiting compounds uptake measured [18F]-fluoro-deoxyglucose experiments. Stimulation tumor-derived different tested revealed complex pattern, whereby survival reducing concentrations varied in experiments more than one order magnitude among tested. We found that could be partially abolished by (i) nicotinic acid (NA) only (NAPRT) expressing (ii) mononucleotide (NMN) all tested, supporting classification these NAMPT inhibitors. In short-time application WZB-117 was lead an almost complete inhibition whereas effect type dependent maximum value ~35% A172, BHY, cells. also inhibited range 25–50%. These data support GLUT inhibitor. Our reveal dual mode action STF-31, serving either or inhibitor, latter seems apparent at higher concentrations. molecular basis such function its appearance previously designated NAMPT-specific requires further investigation.