title: Influence of the carbamate fungicide benomyl on the gene expression and activity of aromatase in the human breast carcinoma cell line MCF-7.
abstract: The carbamate fungicide benomyl reportedly inhibited the growth of the human breast cancer cell line MCF-7 by inducing apoptosis. However, influence of benomyl on the expression and activity of aromatase of MCF-7 cells remains to be examined, since benomyl was identified as an endocrine disruptor. We here confirmed through cell cycle analysis and immunofluorescence staining that benomyl damaged microtubules and caused apoptosis. We also found that benomyl inhibited histone deacetylase (HDAC) 1 and accumulated acetylated histone H3 in MCF-7 cells. Additionally, benomyl enhanced the levels of aromatase protein and mRNA, albeit at high concentrations. It is thus likely that benomyl enhanced the promoter activity of the aromatase gene via acetylation of histone H3 as does the HDAC inhibitor Vorinostat. In conclusion, benomyl remains to be a risk factor as an endocrine disruptor for breast cancer.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: hoechst.atanpe@gmail.com.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawaratani
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: audaciapaula@gmail.com.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuoka
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: y.hirata@gly.oups.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: fukanao0921@gmail.com.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Fukata
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: ynagaoka@kansai-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nagaoka
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. Electronic address: uesato@kansai-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism*; D001542:Benomyl / Q000633:toxicity*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D005659:Fungicides, Industrial / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors / Q000633:toxicity*; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells
chemical_list: D005659:Fungicides, Industrial; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D001141:Aromatase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D001542:Benomyl
keywords: Acetylated histone H3; Benomyl; Carbendazim; Indirect measurement of aromatase activity; Inhibition of HDAC1; MCF-7