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. 2017 Sep 22;7:12221. doi: 10.1038/s41598-017-12557-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(A–C) Metabolite screening by using liquid chromatography-mass spectrometry (LC-MS) on glioblastoma cell lines with or without GLS2 expression after 5-aminolevulinic acid (5-ALA) treatment. Each sample was tested in triplicate. NADPH/NADP levels were significantly increased with GLS2 expression, but they decreased rapidly after 5-ALA treatment in all cell lines (A). GSH/GSSG levels were also decreased after 5-ALA treatment, but they increased with GLS2 expression in 2 cell lines with a relatively small amount of change (B). NADH/NAD levels were decreased after 5-ALA treatment only in cells without GLS2 expression (C). (D) Direct measurement of NADPH/NADP levels in glioblastoma tissues showing different fluorescence intensities (n = 30) confirmed increased NADPH/NADP levels in the no-tumor area without fluorescence.