Kim, Suntae; Jeon, Jang Su; Choi, Yong June; Baek, Ga Hee; Kim, Sang Kyum; Kang, Keon Wook published the artcile< Heterogeneity of glutamine metabolism in acquired-EGFR-TKI-resistant lung cancer>, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is lung cancer glutamine metabolism heterogeneity; Acquired EGFR-TKI-resistant lung cancer; CB-839; CB-839 (Telaglenastat; Glutamine metabolism; PubChem CID: 71577426).
The purpose of this study was to evaluate the heterogeneities of glutamine metabolism in EGFR-TKI-resistant lung cancer cells and its potential as a therapeutic target. Cell proliferation and cell cycle assays was performed by IncuCyte real-time anal. and flow cytometry, resp. Tumor growth was assessed in xenografts implanted with HCC827 GR. An isotopologue anal. was conducted by LC-MS/MS using 13C-(U)-glutamine labeling to determine the amounts of metabolites. Cellular ATP and mitochondrial oxidative phosphorylation were determined by XFp anal. We found that the cell growth of the two acquired EGFR-TKI-resistant lung cancer cells lines (HCC827 GR and H292 ER) depends on glutamine. In HCC827 GR, glutamine deficiency caused reduced GSH synthesis and, subsequently, enhanced ROS generation relative to their parental cells, HCC827. On the other hand, in H292 ER, glutamine mainly acted as a carbon source for TCA-cycle intermediates, and its depletion led to reduced mitochondrial ATP production CB-839, a specific GLS inhibitor, inhibited the latters conversion of glutamine to glutamate and exerted enhanced anti-proliferating effects on the two acquired EGFR-TKI-resistant lung cancer cell lines vs. their parental cell lines. Moreover, oral administration of CB-839 significantly suppressed HCC827 GR tumor growth in the xenograft model. These findings suggest that glutamine dependency in acquired EGFR-TKI-resistant lung cancer is heterogeneous and that inhibition of glutamine metabolism by CB-839 may serve as a therapeutic tool for acquired EGFR-TKI-resistant lung cancer.
Life Sciences published new progress about Antiproliferative agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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