{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["17(6)"],"submitter":["Choi SA"],"pubmed_abstract":["<h4>Background</h4>Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT.<h4>Methods</h4>Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo.<h4>Results</h4>AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH(+) AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH(+) AT/RT cells. Importantly, DSF reduced the metabolism of ALDH(+) AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD(+)/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02).<h4>Conclusion</h4>Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application."],"journal":["Neuro-oncology"],"pagination":["810-21"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4483115"],"repository":["biostudies-literature"],"pubmed_title":["Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors."],"pmcid":["PMC4483115"],"pubmed_authors":["Phi JH","Eum D","Wang KC","Kim IH","Choi SA","Choi JW","Park SH","Kim SK","Lee JY","Park KD"],"additional_accession":[]},"is_claimable":false,"name":"Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors.","description":"<h4>Background</h4>Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT.<h4>Methods</h4>Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo.<h4>Results</h4>AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH(+) AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH(+) AT/RT cells. Importantly, DSF reduced the metabolism of ALDH(+) AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD(+)/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02).<h4>Conclusion</h4>Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jun","modification":"2026-05-07T22:06:41.156Z","creation":"2019-03-27T01:54:09Z"},"accession":"S-EPMC4483115","cross_references":{"pubmed":["25378634"],"doi":["10.1093/neuonc/nou305"]}}