The inhibitory mechanisms of the tyrosine kinase inhibitors herbimycin A, genistein, and tyrphostin B48 with regard to the function of the aryl hydrocarbon receptor in caco-2 cells

Shuya Kasai, Hideaki Kikuchi

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by dioxin and related xenobiotics. Although the activation of AhR is inhibited by tyrosine kinase inhibitors, the molecular mechanism has not been clarified. In the current study, the inhibitory mechanisms of several inhibitors of tyrosine kinase, herbimycin A, genistein, and tyrphostin B48, on AhR activation was analyzed in human Caco-2 cells. All the inhibitors suppressed the transcriptional activation of AhR induced by 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD). Herbimycin A induced down-regulation of the AhR protein by inhibiting its molecular chaperone heat shock protein 90 (HSP90). In contrast, genistein and tyrphostin B48 inhibited the nuclear localization of AhR induced by TCDD, although the amount of AhR protein was not altered. The inhibitory effects of genistein and tyrphostin B48 on endogenous tyrosine kinase activity were evaluated by detection of alterations in the tyrosine phosphorylation states of cellular proteins.

    Original languageEnglish
    Pages (from-to)36-43
    Number of pages8
    JournalBioscience, Biotechnology and Biochemistry
    Volume74
    Issue number1
    DOIs
    Publication statusPublished - 2010

    Keywords

    • Aryl hydrocarbon receptor (AhR)
    • Heat shock protein 90 (HSP90)
    • Yrosine kinase inhibitor

    ASJC Scopus subject areas

    • Biotechnology
    • Analytical Chemistry
    • Biochemistry
    • Applied Microbiology and Biotechnology
    • Molecular Biology
    • Organic Chemistry

    Fingerprint Dive into the research topics of 'The inhibitory mechanisms of the tyrosine kinase inhibitors herbimycin A, genistein, and tyrphostin B48 with regard to the function of the aryl hydrocarbon receptor in caco-2 cells'. Together they form a unique fingerprint.

    Cite this