Peroxynitrite is involved in the mitochondrial dysfunction induced by Sorafenib in liver cancer cells.

• Tác giả: Susana Cadenas, Marta Casado, Patricia de la Cruz-Ojeda, Marina Fuertes-Agudo, Guillermo López-Lluch, Ana Mata, Jordi Muntané, Elena Navarro-Villarán, Plácido Navas
• Ngôn ngữ: eng
• Ký hiệu phân loại: 553.453 Tin
• Thông tin xuất bản: United States : Free radical biology & medicine , 2025
• Bộ sưu tập: NCBI
• ID: 496338

Tóm tắt

BACKGROUND: Sorafenib is a tyrosine kinase inhibitor (TKI) that belongs to the landscape of treatments for advanced stages of hepatocellular carcinoma (HCC). The induction of cell death and cell cycle arrest by Sorafenib has been associated with mitochondrial dysfunction in liver cancer cells. Our research aim was to decipher underlying oxidative and nitrosative stress induced by Sorafenib leading to mitochondrial dysfunction in liver cancer cells. METHODS: MnTBAP, catalase and the scavenger of peroxynitrite FeTPPs were administered to Sorafenib (0-10 μM)-treated HepG2 cells. Oxygen consumption and glycolytic flux were determined in cultured cells. Mitochondrial complex activities were measured in mitochondrial fraction and cell lysates. The protein and mRNA expression of subunits of electron transport chain (ETC) were assessed by immunoblot and RNA-seq. RESULTS: Sorafenib (10 μM) increased nitric oxide (NO) and superoxide anion (O CONCLUSIONS: The induction of cell death by Sorafenib was associated with peroxynitrite generation, which impacted the expression of ETC subunits and mitochondrial functionality in liver cancer cells.