nsc-600032 and Liver-Neoplasms

nsc-600032 has been researched along with Liver-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for nsc-600032 and Liver-Neoplasms

ArticleYear
Combretastatin A-1 phosphate, a microtubule inhibitor, acts on both hepatocellular carcinoma cells and tumor-associated macrophages by inhibiting the Wnt/β-catenin pathway.
    Cancer letters, 2016, 09-28, Volume: 380, Issue:1

    Combretastatin A-1 phosphate (CA1P) is a microtubule polymerization inhibitor that binds to the colchicine-binding site of tubulin. We demonstrated that CA1P has outstanding anti-cancer activity against hepatocellular carcinoma (HCC) in vitro and in vivo. As determined by fluorescence staining and western blots (WBs), CA1P induced reactive oxygen species (ROS) accumulation and apoptosis in HepG2 cells with a down-regulation of Mcl-1. Additional studies indicated that CA1P induced microtubule depolymerization-mediated AKT inactivation, which resulted in GSK-3β activation, Wnt/β-Catenin pathway inhibition, and Mcl-1 down-regulation. The induction of HepG2 cell apoptosis by CA1P was prevented by a GSK-3β-specific inhibitor. Furthermore, immunohistochemistry studies on hepatocellular carcinoma mouse models showed that CA1P had activity against tumor-associated macrophages (TAMs). CA1P induced TAM apoptosis in vitro through the same mechanism observed with HepG2 cells, and it eliminated TAMs in the tumor microenvironment (TME) in vivo. In TME, the expression of TGF-β and TNF-α was also altered. The adoptive transfer of macrophages partly rescued the growth of tumor inhibited by CA1P. These findings indicate that CA1P has great potential to impact both cancer cells and the microenvironment, and our results should accelerate the application of CA1P for HCC therapy in clinic.

    Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Dose-Response Relationship, Drug; Glycogen Synthase Kinase 3 beta; Hep G2 Cells; Humans; Inhibitory Concentration 50; Liver Neoplasms; Macrophages; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Stilbenes; Transforming Growth Factor beta; Tubulin Modulators; Tumor Burden; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Wnt Signaling Pathway; Xenograft Model Antitumor Assays

2016
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