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Glutathione inhibits lung cancer development by reducing interleukin-6 expression and reversing the Warburg effect.
Fan, Chenchen; Chen, Guojie; Reiter, Russel J; Bai, Yidong; Zheng, Tiansheng; Fan, Lihong.
Afiliación
  • Fan C; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
  • Chen G; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
  • Reiter RJ; Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
  • Bai Y; Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
  • Zheng T; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
  • Fan L; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: 1300008@t
Mitochondrion ; 79: 101953, 2024 Aug 29.
Article en En | MEDLINE | ID: mdl-39214486
ABSTRACT
Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticancer effect of GSH in patients with pulmonary nodules. Thirty patients with pulmonary nodules were treated with GSH intravenously for 10 days at a dose of 1.8 g/d, followed by oral administration of the drug at a dose of 0.4 g three times daily for 6 months. The results showed that GSH treatment promoted nodule absorption and reduced the IL-6 level in the peripheral blood of the patients. GSH reduced IL-6 expression in inflammatory BEAS-2B and lung cancer cells and inhibited the proliferation of lung cancer cell lines in vitro. In addition, GSH reduced IL-6 expression by decreasing ROS via down-regulating PI3K/AKT/FoxO pathways. Finally, GSH reversed the Warburg effect, restored mitochondrial function, and reduced the IL-6 expression via PI3K/AKT/FoxO pathways. The in vivo experiment confirmed that GSH inhibited lung cancer growth, improved mitochondrial function, and reduced the IL-6 expression by regulating key enzymes via the PI3K/AKT/FoxO pathway. In conclusion, we uncovered that GSH exerts an unprecedentedly potent anti-cancer effect to prevent the transformation of lung nodules to lung cancer by improving the mitochondrial function and suppressing inflammation via PI3K/AKT/FoxO pathway. This investigation innovatively positions GSH as a potentially safe and efficacious old drug with new uses, inhibiting inflammation and early lung cancer. The use of the drug offers a promising preventive strategy when administered during the early stages of lung cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mitochondrion Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mitochondrion Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos