Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells

DOI Web Site 被引用文献4件
  • Sangkil Nam
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Ralf Buettner
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • James Turkson
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Donghwa Kim
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Jin Q. Cheng
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Stephan Muehlbeyer
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Frankie Hippe
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Sandra Vatter
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Karl-Heinz Merz
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Gerhard Eisenbrand
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany
  • Richard Jove
    Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612; Department of Pathology, University of South Florida College of Medicine, Tampa, FL 33612; and Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin Schrödinger Strasse 52, 67663 Kaiserslautern, Germany

書誌事項

公開日
2005-04-18
DOI
  • 10.1073/pnas.0409467102
公開者
National Academy of Sciences

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説明

<jats:p> Stat3 protein has an important role in oncogenesis and is a promising anticancer target. Indirubin, the active component of a traditional Chinese herbal medicine, has been shown previously to inhibit cyclin-dependent kinases, resulting in cell cycle arrest. Here, we show that the indirubin derivatives E564, E728, and E804 potently block constitutive Stat3 signaling in human breast and prostate cancer cells. In addition, E804 directly inhibits Src kinase activity (IC <jats:sub>50</jats:sub> = 0.43 μM) in an <jats:italic>in vitro</jats:italic> kinase assay. Levels of tyrosyl phosphorylation of c-Src are also reduced in cultured cells 30 min after E804 treatment. Tyrosyl phosphorylation of Stat3, which is known to be phosphorylated by c-Src, was decreased, and constitutive Stat3 DNA binding-activity was suppressed in cells 30 min after E804 treatment. The antiapoptotic proteins Mcl-1 and Survivin, which are encoded in target genes of Stat3, were down-regulated by indirubin derivatives, followed by induction of apoptosis. These results demonstrate that E804 directly blocks the Src-Stat3 signaling pathway, suggesting that the antitumor activity of indirubin compounds is at least partially due to inhibition of this pathway. </jats:p>

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