A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC–OXPHOS axis

• DOI: 10.1186/s12967-023-04349-3
• Publication Date: 2023-07-26T19:03:18Z
• Authors: Ruibin Jiang; Zhongjian Chen; Maowei Ni; Xia Li; Hangjie Ying; Jianguo Fen; Danying Wan; Chanjuan Peng; Wei Zhou; Linhui Gu
• Keywords: Ovarian Neoplasms; Research; Gossypol acetic acid; R; Oxidative Phosphorylation; 3. Good health; Mitochondria; Neoplasm Proteins; LRPPRC; Disease Models, Animal; Ovarian cancer; Cell Line, Tumor; Neoplastic Stem Cells; Medicine; Animals; Humans; Oxidative phosphorylation; Female; Cell Proliferation

Ovarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), enables cell growth, migration, stem maintenance, a critical driver of disease progression potential intervention target OC. However, current OXPHOS strategy mainly suppresses activity electron transport chain directly cannot effectively distinguish normal tissues from tissues, resulting in serious side effects efficacy.We screened natural product libraries to investigate anti-OC that OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch xenograft model was applied evaluate anti-tumor mechanism small molecules obtained by screening OC.Gossypol acetic acid (GAA), widely used medicine, out drug library with function suppressing OC targeting leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes synthesis subunits binding RNAs encoded DNA. GAA binds induces rapid degradation ubiquitin-independent manner. overexpressed OC, highly correlated poor outcomes could promote phenotype cells vitro vivo. management inhibits clonal formation, maintenance vitro, subcutaneous graft growth vivo.Our study identified provided corresponding inhibitor OXPHOS-based therapy. complex via protein, supporting its utility as agent ovarian cancer.