Research article summary (published 30 Aug 2009):

Involvement of N-acetyltransferase human in the cytotoxic activity of 5-fluorouracil.

Full Abstract

N-acetyltransferase human (NATH) participates in a posttranslational modification of the proteins and has been reported to play a role in apoptosis. In this study, the involvement of NATH in the cytotoxic action of 5-fluorouracil (5-FU) in human squamous cell carcinoma HEp-2 cells was examined. We found that 5-FU decreased NATH expression in a dose-dependent and time-dependent manner. No change was observed after treatment with bleomycin, nedaplatin, mitomycin C, or methotrexate. Interestingly, knockdown of NATH by small interfering RNA resulted in the downregulation of thymidylate synthase mRNA expression and induced apoptosis. Conversely, NATH overexpression facilitated cell proliferation independent of the presence of 5-FU. The effect of NATH knockdown on the expression of proteins in HEp-2 cells was examined using two-dimensional gel electrophoresis and mass spectrometry. Profilin 1, CutA, ras-related nuclear protein, annexin A5, enolase 1, and elongation factor 1 alpha 1 were found to be upregulated and 14-3-3eta, tublin, nuclear auto antigenic sperm protein, heat shock protein 70, and heat shock protein 90 were downregulated by knockdown of NATH. The results of this study suggest that NATH plays an important role in the cytotoxic activity of 5-FU.

Author information

Author/s: Takubo, Kazuko (K); Tsuchiya, Hiroyuki (H); Kurimasa, Akihiro (A); Arnesen, Thomas (T); Ryoke, Kazuo (K); Shiota, Goshi (G);

Affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Nishimachi 36-1, Yonago 683-8504, Japan. kazuko(-atsign-)med.tottori-u.ac.jp

Journal and publication information

Publication Type: Journal Article

Journal: Anti-cancer drugs (Anticancer Drugs), published in England. (Language: eng)

Reference: 2009-Sep; vol 20 (issue 8) : pp 668-75

Dates: Created 2009/07/24; Completed 2009/10/16;

PMID: 19561488, status: MEDLINE (last retrieval date: 10/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Antineoplastic Agents - pharmacology Apoptosis - drug effects; genetics Arylamine N-Acetyltransferase - genetics; metabolism Caspase 9 - metabolism Cell Cycle - drug effects Cell Death - drug effects; genetics Cell Line, Tumor Down-Regulation - drug effects Fluorouracil - pharmacology; toxicity Gene Expression - drug effects; genetics

Gene Expression - drug effects; genetics Humans Isoenzymes - genetics; metabolism Poly(ADP-ribose) Polymerases - metabolism Protein Biosynthesis - drug effects Proteins - metabolism RNA, Small Interfering - genetics Thymidylate Synthase - genetics Transfection Up-Regulation - drug effects

Associated Chemicals: Antineoplastic Agents (0) ; Isoenzymes (0) ; Proteins (0) ; RNA, Small Interfering (0) ; Fluorouracil (51-21-8) ; Thymidylate Synthase (EC 2.1.1.45) ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; N-acetyltransferase 1 (EC 2.3.1.5) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Caspase 9 (EC 3.4.22.-)

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