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- W2903039717 abstract "Human liver cancer HepG2 cell line is β-catenin mutated and exhibits features of glutamine addiction. HepG2 cells in culture are sensitive to glutamine starvation induced with L-asparaginase from Erwinia chrysanthemi (ASNase) and the inhibitor of Glutamine Synthetase (GS) methionine-L-sulfoximine (MSO). To evaluate HepG2 behaviour in vivo, 8-day subcutaneous HepG2 xenografts were treated for three weeks with ASNase, MSO, or both. The administration of ASNase and MSO produced a marked serum depletion of both asparagine and glutamine, a decrease in liver and tumor glutamine content, and the inhibition of liver GS activity without any evidence of systemic toxicity. Xenograft growth was significantly hindered by either ASNase or MSO and completely prevented by the combined treatment. Histopathological evaluation confirmed high GS expression and nuclear positivity for β-catenin in HepG2 xenografts, as well as the inhibition of tumor growth in mice treated with both ASNase and MSO. These results strengthen the hypothesis that liver cancers carrying β-catenin mutations are glutamine-addicted and represent the first evidence for antitumor activity of GS inhibitors." @default.
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- W2903039717 date "2013-04-01" @default.
- W2903039717 modified "2023-09-23" @default.
- W2903039717 title "Drug‐induced glutamine depletion hinders the growth of β‐ catenin mutated human liver cancer xenografts" @default.
- W2903039717 doi "https://doi.org/10.1096/fasebj.27.1_supplement.387.9" @default.
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