Coptisine suppresses pulmonary nodule carcinogenesis by inducing CAFs mitochondrial apoptosis via Sirt3/YME1L1

Coptisine, an active alkaloid from Coptis chinensis , exhibits potent anticancer effects by targeting cancer-associated fibroblasts (CAFs) in the tumor microenvironment. This study investigates its mechanism in attenuating lung via Sirt3-mediated deacetylation of YME1L1, regulating mitochondrial apoptosis in CAFs. Orthotopic lung cancer models were established in C57BL/6 mice using SCLC-2 cells, treated with Coptisine (60 or 120 mg/kg/day). In vitro, primary pulmonary fibroblasts (CAFs) co-cultured with SCLC-2 cells were assessed for proliferation (CCK-8), metastasis (Transwell), apoptosis (ELISA), mitochondrial potential (JC-1), and ROS (DCFH-DA). Coptisine inhibited tumor growth, improved lung function, and reduced myofibroblast markers (α-SMA, FAP). It upregulated Bax and Sirt3 while downregulating YME1L1, BCL-2, and EMT proteins (e.g., Vimentin), damaging to mitochondrial function. Mechanistically, Coptisine activated Sirt3 to deacetylate YME1L1, inducing mitochondrial fragmentation in CAFs. These findings highlight Coptisine's potential as a lung cancer therapy by targeting the Sirt3/YME1L1 pathway in CAFs.