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<p>To explore the effect of Licochalcone A on cuproptosis in glioma and the underlying mechanism, U87 MG and U251 cells were treated with 10, 20, and 30 µM Licochalcone A for 24&#xa0;h. Key assays including immunofluorescence, TEM, mitochondrial membrane potential and morphological analysis, as well as other cuproptosis-related indexes were detected. Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used. An in vivo nude mouse xenograft model was established. Our results demonstrated that Licochalcone A triggered cuproptosis in a dose-dependent manner, and in U87 and U251 cells, 30 µM Licochalcone A treatment increased the Cu²⁺ accumulation by 2.86 ± 0.67 folds and 1.96 ± 0.39 folds, elevated pyruvic acid levels by 2.15 ± 0.23 folds and 2.57 ± 0.46 folds, reduced mitochondrial membrane potential by 34.13 ± 1.70% and 40.43 ± 9.05%, downregulated the protein expression of FDX1 and LIAS, and increased cellular ROS levels by 4.74 ± 0.85 folds and 5.10 ± 2.16 folds, respectively. These changes were accompanied by obvious mitochondrial swelling and cristae disruption, resulting in a significant inhibition of cell proliferation. Mechanistically, it promoted cuproptosis by inactivating RAS/ERK. In vivo, 10&#xa0;mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.</p>

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Licochalcone a Disrupted Mitochondrial Function to Promote Cuproptosis in Glioblastoma Through Regulating RAS/MAPK Pathway

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Fengfeng Zhou,
  • Chenglin Li,
  • Fengyuan Che

摘要

To explore the effect of Licochalcone A on cuproptosis in glioma and the underlying mechanism, U87 MG and U251 cells were treated with 10, 20, and 30 µM Licochalcone A for 24 h. Key assays including immunofluorescence, TEM, mitochondrial membrane potential and morphological analysis, as well as other cuproptosis-related indexes were detected. Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used. An in vivo nude mouse xenograft model was established. Our results demonstrated that Licochalcone A triggered cuproptosis in a dose-dependent manner, and in U87 and U251 cells, 30 µM Licochalcone A treatment increased the Cu²⁺ accumulation by 2.86 ± 0.67 folds and 1.96 ± 0.39 folds, elevated pyruvic acid levels by 2.15 ± 0.23 folds and 2.57 ± 0.46 folds, reduced mitochondrial membrane potential by 34.13 ± 1.70% and 40.43 ± 9.05%, downregulated the protein expression of FDX1 and LIAS, and increased cellular ROS levels by 4.74 ± 0.85 folds and 5.10 ± 2.16 folds, respectively. These changes were accompanied by obvious mitochondrial swelling and cristae disruption, resulting in a significant inhibition of cell proliferation. Mechanistically, it promoted cuproptosis by inactivating RAS/ERK. In vivo, 10 mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.