A new strategy for the treatment of glioma by intervention glutathione metabolism is proposed

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Dalian Institute of Chemical Physics researcher
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glioma is the most common primary brain tumor, IDH1 mutation is one of the most common pathogenic mutations, but there is currently no choice of treatment for IDH1 mutation glioma. To address this problem, the researchers found that glutathione anabolic path paths are active in cancer cells with IDH1 mutations. Glutathione anabolism is regulated by Nrf2 transcription factors and is an important antioxidant metabolic pathway. In-body studies have found that inhibiting the transcriptional activity of Nrf2 can reduce the synthesis of glutathione, resulting in the apoptosis of cancer cells with IDH1 mutations. Based on this finding, the team proposed a new strategy to inhibit the metabolic pathway of glutathione to treat IDH1 mutant glioma.
, a compound derived from Retolide, is an effective Nrf2 inhibitor. In vitro and in vivo models, it was found that in IDH1 mutant glioma cells, the transcription activity of Nrf2 was inhibited, and the expression of important genes (GCLC, GCLM and SLC7A11) in the glutathione synthesis pathline was reduced, thus destroying glutathione metabolism and increasing oxidative damage in cells, leading to apoptosis.
this study expounds the importance of inhibiting the Glutathione metabolic pathrain regulated by Nrf2 for tumor therapy, and provides a new way of thinking for the treatment of malignant tumors with IDH1 mutation. (Source: Liu Wansheng Yudi, China Science Journal)
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