ArticleJournal of translational medicine2023
A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Toxicity reduction and immune reconstitution with adjuvant traditional Chinese medicine for postoperative ovarian cancer: a systematic review and meta-analysis.Frontiers in medicine · 2026Pooled it
- Metabolic vulnerabilities in ovarian cancer decoding the nexus between nutrient adaptation and therapy resistance.Journal of advanced research · 2026Review
- Mfn1-mediated imbalanced mitochondrial dynamics promotes ovarian cancer stemness by inducing metabolic reprogramming.Journal of physiology and biochemistry · 2026Article
- Synergistic Anti-Tumor Activity of LRPPRC Inhibition and Dasatinib Through Dual Oxidative Phosphorylation Disruption.Pharmaceuticals (Basel, Switzerland) · 2026Article
- LRPPRC-Driven Oxidative Phosphorylation Is Associated with Elesclomol-Induced Cuproptosis in Ovarian Cancer.International journal of molecular sciences · 2025Article
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Effects of Gossypol Exposure on Ovarian Reserve Function: Comprehensive Risk Assessment Based on TRAEC Strategy.Toxics · 2025Article
- An RNA transmethylation pathway governs kidney nephrogenic potential.Nature communications · 2025Article
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Lactic acid metabolism: gynecological cancer's Achilles' heel.Discover oncology · 2025Review
- SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer.Oncology letters · 2025Article
- Transcriptome analysis of the effect of HERV-K env gene knockout in ovarian cancer cell lines.Genes & genomics · 2024Article
- Readers of RNA Modification in Cancer and Their Anticancer Inhibitors.Biomolecules · 2024Review
- Article
- The Biological Role of LRPPRC in Human Cancers.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOvarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), which enables cell growth, migration, and cancer stem cell maintenance, is a critical driver of disease progression and a potential intervention target of OC. However, the current OXPHOS intervention strategy mainly suppresses the activity of the electron transport chain directly and cannot effectively distinguish normal tissues from cancer tissues, resulting in serious side effects and limited efficacy.
methodsWe screened natural product libraries to investigate potential anti-OC drugs that target OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch assay, and xenograft model was applied to evaluate the anti-tumor mechanism of small molecules obtained by screening in OC.
resultsGossypol acetic acid (GAA), a widely used gynecological medicine, was screened out from the drug library with the function of suppressing OXPHOS and OC progression by targeting the leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. GAA binds to LRPPRC directly and induces LRPPRC rapid degradation in a ubiquitin-independent manner. LRPPRC was overexpressed in OC, which is highly correlated with the poor outcomes of OC and could promote the malignant phenotype of OC cells in vitro and in vivo. GAA management inhibits cell growth, clonal formation, and cancer stem cell maintenance in vitro, and suppresses subcutaneous graft tumor growth in vivo.
conclusionsOur study identified a therapeutic target and provided a corresponding inhibitor for OXPHOS-based OC therapy. GAA inhibits OC progression by suppressing OXPHOS complex synthesis via targeting LRPPRC protein, supporting its potential utility as a natural therapeutic agent for ovarian cancer.
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