4-methylene-2-octyl-5-oxofuran-3-carboxylic-acid has been researched along with Liver-Neoplasms* in 3 studies
3 other study(ies) available for 4-methylene-2-octyl-5-oxofuran-3-carboxylic-acid and Liver-Neoplasms
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Novel lysophosphatidic acid receptor 6 antagonists inhibit hepatocellular carcinoma growth through affecting mitochondrial function.
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. Topics: 4-Butyrolactone; Acetates; Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Mice, Nude; Mitochondria; Receptors, Lysophosphatidic Acid | 2020 |
Growth arrest induced by C75, A fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma.
C75, a well-known fatty acid synthase (FAS) inhibitor, has been shown to possess potent anti-cancer activity in vitro and in vivo. In this study, we reveal that C75 is a cell cycle arrest inducer and explore the potential mechanisms for this effect in hepatocellular carcinoma (HCC) cell lines with abundant FAS expression: HepG2 and SMMC7721 cells with wt-p53, and Hep3B cells with null p53. The results showed FAS protein expression and basal activity levels were higher in HepG2 cells than in the other two HCC cell lines. Treatment with C75 inhibited FAS activity within 30 min of administration and induced G(2) phase arrest accompanied by p53 overexpression in HepG2 and SMMC7721 cells. By contrast, C75 triggered G(1) phase arrest in Hep3B cells, and RNA interference targeting p53 did not attenuate C75-induced G(2) arrest in HepG2 cells. Similarly, p53 overexpression via p53 plasmid transfection did not affect C75-induced G(1) phase arrest in Hep3B cells. However, we observed a clear correlation between p38 MAPK activation triggered by C75 and the induction of cell cycle arrest in all three HCC cells. Furthermore, treatment with the p38 MAPK inhibitor SB203580 reduced p38 MAPK activity and cell cycle arrest, and also partially restored cyclin A, cyclin B1, cyclin D1 and p21 protein levels. Collectively, it was p38 MAPK but not p53 involved in C75-mediated tumor cell growth arrest in HCC cells. Topics: 4-Butyrolactone; Blotting, Western; Carcinoma, Hepatocellular; Cell Proliferation; Cyclin A; Cyclin B; Cyclin B1; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; fas Receptor; Fatty Acid Synthases; Flow Cytometry; G2 Phase; Humans; Immunoprecipitation; Liver Neoplasms; p38 Mitogen-Activated Protein Kinases; Plasmids; RNA, Small Interfering; Tumor Cells, Cultured; Tumor Suppressor Protein p53 | 2006 |
Cancer therapy: back to metabolism.
Topics: 4-Butyrolactone; Carcinoma, Hepatocellular; Cell Cycle; fas Receptor; Fatty Acid Synthases; Fatty Acids; Humans; Liver Neoplasms; p38 Mitogen-Activated Protein Kinases; Tumor Suppressor Protein p53 | 2006 |