Paclitaxel inhibits N-acetyltransferase activity and gene expression in human stomach tumor cells (SC-M1)

Te-Chun Hsia, Jen Hung Yang, Hui Ju Lin, Chun Shu Yu, Fu Shun Yu, Jing-Gung Chung

    Research output: Contribution to journalArticle

    4 Scopus citations

    Abstract

    Evidence has shown that N-acetyltransferase (NAT) acetylated 2-aminofluorene (AF) to form N-acetyl-2-aminofluorene (AAF). Then it was metabolized by cytochrome P450 (CYP) enzyme to form ring or N-hydroxylated metabolites. Sulfotransferase and other enzymes participated to form the ultimate metabolites which bind to DNA to form DNA-AF adducts which may have led to cancer development. The aim of the present study is to demonstrate whether paclitaxel (taxol) can inhibit the NAT activity, NAT gene expression and DNA-AF adduct formation in human stomach tumor cell line (SC-M1). The activity of NAT was determined by high performance liquid chromatography (HPLC) assaying for the amounts of acetylated AF (AAF) or p-aminobenzoic acid (N-Ac-PABA) and nonacetylated AF or PABA. While SC-M1 cell cytosols were used for examining NAT activity, intacts cells were used for examining all three: NAT activity, gene expression and DNA-AF adduct formation. As compared with the control group, the paclitaxel- treated group showed decreased NAT activity and DNA-AF adduct formation in SC-M1 cells and the decrease was dose-dependent. The results also indicated that paclitaxel decreased the apparent values of Km and Vmax from SC-M1 cells in both cytosol and intact cells. Palitaxel did significantly affect NAT gene expression (NAT1 mRNA) in SC-M1 cells.

    Original languageEnglish (US)
    Pages (from-to)21-38
    Number of pages18
    JournalResearch Communications in Molecular Pathology and Pharmacology
    Volume115-116
    StatePublished - Dec 1 2004

    Keywords

    • 2-aminofluorene
    • DNA adduct
    • Human stomach cancer cell line (SC-M1)
    • N-acetyltransferase
    • Paclitaxel

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

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