Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G(2)/M phase cell cycle arrest, DNA damage, and G(2)/M checkpoint activation

J M Visanji, Susan Joyce Duthie, Lynn Peters Pirie, D G Thompson, P J Padfield

    Research output: Contribution to journalArticle

    52 Citations (Scopus)

    Abstract

    Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals present in substantial concentrations in edible vegetables of the genus Brassica, were investigated for their effects on Caco-2 cell proliferation. Benzyl and phenethyl isothiocyanate inhibited DNA synthesis, with 50% inhibitory concentrations of 5.1 and 2.4 mumol/L, respectively, and significantly increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h: respectively. There was no adverse effect of either chemical on cell viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48 h in cells synchronized at prometaphase with nocodazole and subsequently treated with 10 mumol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl and phenethyl isothiocyanate increased DNA strand breakage, increased phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21 expression. These results suggest that the antiproliferative effects of benzyl and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be maintained through upregulation of p21. This study indicates that some dietary isothiocyanates may exert an anti proliferative effect through activation of the G(2)/M DNA damage checkpoint.

    Original languageEnglish
    Pages (from-to)3121-3126
    Number of pages6
    JournalThe Journal of Nutrition
    Volume134
    Issue number11
    Publication statusPublished - Nov 2004

    Keywords

    • isothiocyanates
    • proliferation
    • DNA damage
    • checkpoints
    • PHENETHYL ISOTHIOCYANATE
    • BENZYL ISOTHIOCYANATE
    • CANCER CELLS
    • PHENYLETHYL ISOTHIOCYANATE
    • CRUCIFEROUS VEGETABLES
    • OXIDIZED PYRIMIDINES
    • INDUCED APOPTOSIS
    • STRAND BREAKS
    • P53
    • P21
    • checkpoints

    Cite this

    Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G(2)/M phase cell cycle arrest, DNA damage, and G(2)/M checkpoint activation. / Visanji, J M ; Duthie, Susan Joyce; Pirie, Lynn Peters; Thompson, D G ; Padfield, P J .

    In: The Journal of Nutrition, Vol. 134, No. 11, 11.2004, p. 3121-3126.

    Research output: Contribution to journalArticle

    Visanji, J M ; Duthie, Susan Joyce ; Pirie, Lynn Peters ; Thompson, D G ; Padfield, P J . / Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G(2)/M phase cell cycle arrest, DNA damage, and G(2)/M checkpoint activation. In: The Journal of Nutrition. 2004 ; Vol. 134, No. 11. pp. 3121-3126.
    @article{dba8c437a4b24c398ce767c582eaeed3,
    title = "Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G(2)/M phase cell cycle arrest, DNA damage, and G(2)/M checkpoint activation",
    abstract = "Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals present in substantial concentrations in edible vegetables of the genus Brassica, were investigated for their effects on Caco-2 cell proliferation. Benzyl and phenethyl isothiocyanate inhibited DNA synthesis, with 50{\%} inhibitory concentrations of 5.1 and 2.4 mumol/L, respectively, and significantly increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h: respectively. There was no adverse effect of either chemical on cell viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48 h in cells synchronized at prometaphase with nocodazole and subsequently treated with 10 mumol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl and phenethyl isothiocyanate increased DNA strand breakage, increased phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21 expression. These results suggest that the antiproliferative effects of benzyl and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be maintained through upregulation of p21. This study indicates that some dietary isothiocyanates may exert an anti proliferative effect through activation of the G(2)/M DNA damage checkpoint.",
    keywords = "isothiocyanates, proliferation, DNA damage, checkpoints, PHENETHYL ISOTHIOCYANATE, BENZYL ISOTHIOCYANATE, CANCER CELLS, PHENYLETHYL ISOTHIOCYANATE, CRUCIFEROUS VEGETABLES, OXIDIZED PYRIMIDINES, INDUCED APOPTOSIS, STRAND BREAKS, P53, P21, checkpoints",
    author = "Visanji, {J M} and Duthie, {Susan Joyce} and Pirie, {Lynn Peters} and Thompson, {D G} and Padfield, {P J}",
    year = "2004",
    month = "11",
    language = "English",
    volume = "134",
    pages = "3121--3126",
    journal = "The Journal of Nutrition",
    issn = "0022-3166",
    publisher = "American Society for Nutrition",
    number = "11",

    }

    TY - JOUR

    T1 - Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G(2)/M phase cell cycle arrest, DNA damage, and G(2)/M checkpoint activation

    AU - Visanji, J M

    AU - Duthie, Susan Joyce

    AU - Pirie, Lynn Peters

    AU - Thompson, D G

    AU - Padfield, P J

    PY - 2004/11

    Y1 - 2004/11

    N2 - Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals present in substantial concentrations in edible vegetables of the genus Brassica, were investigated for their effects on Caco-2 cell proliferation. Benzyl and phenethyl isothiocyanate inhibited DNA synthesis, with 50% inhibitory concentrations of 5.1 and 2.4 mumol/L, respectively, and significantly increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h: respectively. There was no adverse effect of either chemical on cell viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48 h in cells synchronized at prometaphase with nocodazole and subsequently treated with 10 mumol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl and phenethyl isothiocyanate increased DNA strand breakage, increased phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21 expression. These results suggest that the antiproliferative effects of benzyl and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be maintained through upregulation of p21. This study indicates that some dietary isothiocyanates may exert an anti proliferative effect through activation of the G(2)/M DNA damage checkpoint.

    AB - Benzyl isothiocyanate and phenethyl isothiocyanate, two aromatic phytochemicals present in substantial concentrations in edible vegetables of the genus Brassica, were investigated for their effects on Caco-2 cell proliferation. Benzyl and phenethyl isothiocyanate inhibited DNA synthesis, with 50% inhibitory concentrations of 5.1 and 2.4 mumol/L, respectively, and significantly increased the doubling times of Caco-2 cells from 32 h to 220 and 120 h: respectively. There was no adverse effect of either chemical on cell viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, but benzyl isothiocyanate and phenethyl isothiocyanate both caused an accumulation of cells in the G(2)/M phase of the cell cycle, which was maintained for at least 48 h in cells synchronized at prometaphase with nocodazole and subsequently treated with 10 mumol/L benzyl isothiocyanate or phenethyl isothiocyanate. Both benzyl and phenethyl isothiocyanate increased DNA strand breakage, increased phosphorylation of the G(2)/M checkpoint enforcer Chk2, and induced p21 expression. These results suggest that the antiproliferative effects of benzyl and phenethyl isothiocyanates toward Caco-2 cells are due at least in part to the activation of the G(2)/M DNA damage checkpoint, and that sustained G(2)/M phase cell cycle arrest in response to benzyl and phenethyl isothiocyanates may be maintained through upregulation of p21. This study indicates that some dietary isothiocyanates may exert an anti proliferative effect through activation of the G(2)/M DNA damage checkpoint.

    KW - isothiocyanates

    KW - proliferation

    KW - DNA damage

    KW - checkpoints

    KW - PHENETHYL ISOTHIOCYANATE

    KW - BENZYL ISOTHIOCYANATE

    KW - CANCER CELLS

    KW - PHENYLETHYL ISOTHIOCYANATE

    KW - CRUCIFEROUS VEGETABLES

    KW - OXIDIZED PYRIMIDINES

    KW - INDUCED APOPTOSIS

    KW - STRAND BREAKS

    KW - P53

    KW - P21

    KW - checkpoints

    M3 - Article

    VL - 134

    SP - 3121

    EP - 3126

    JO - The Journal of Nutrition

    JF - The Journal of Nutrition

    SN - 0022-3166

    IS - 11

    ER -