ArticleJournal of molecular medicine (Berlin, Germany)2020
Novel lysophosphatidic acid receptor 6 antagonists inhibit hepatocellular carcinoma growth through affecting mitochondrial function.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism.Oncology research · 2025Article
- Lysophosphatidic acid promotes endometrial decidualization in recurrent implantation failure patients by regulating LPAR6.Frontiers in cell and developmental biology · 2025Article
- Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy.International journal of molecular sciences · 2023Review
- Advancements in Hepatocellular Carcinoma: Potential Preclinical Drugs and their Future.Current pharmaceutical design · 2023Review
- Lysophosphatidic acid signaling via LPAJournal of neurochemistry · 2022Article
- Review
- Roles of Autotaxin/Autotaxin-Lysophosphatidic Acid Axis in the Initiation and Progression of Liver Cancer.Frontiers in oncology · 2022Review
- Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8Cell reports · 2021Article
- Review
- Review
- The perplexity of targeting genetic alterations in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2020Article
- Recent progress in treatment of hepatocellular carcinoma.American journal of cancer research · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and the commonest liver cancer. It is expected to become the third leading cause of cancer-related deaths in Western countries by 2030. Effective pharmacological approaches for HCC are still unavailable, and the currently approved systemic treatments are unsatisfactory in terms of therapeutic results, showing many side effects. Thus, searching for new effective and nontoxic molecules for HCC treatment is of paramount importance. We previously demonstrated that lysophosphatidic acid (LPA) is an important contributor to the pathogenesis of HCC and that lysophosphatidic acid receptor 6 (LPAR6) actively supports HCC tumorigenicity. Here, we screened for novel LPAR6 antagonists and found that two compounds, 4-methylene-2-octyl-5-oxotetra-hydrofuran-3-carboxylic acid (C75) and 9-xanthenylacetic acid (XAA), efficiently inhibit HCC growth, both in vitro and in vitro, without displaying toxic effects at the effective doses. We further investigated the mechanisms of action of C75 and XAA and found that these compounds determine a G1-phase cell cycle arrest, without inducing apoptosis at the effective doses. Moreover, we discovered that both molecules act on mitochondrial homeostasis, by increasing mitochondrial biogenesis and reducing mitochondrial membrane potential. Overall, our results show two newly identified LPAR6 antagonists with a concrete potential to be translated into effective and side effect-free molecules for HCC therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.