Tags

Type your tag names separated by a space and hit enter

Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium.
J Nutr. 2001 Dec; 131(12):3294-302.JN

Abstract

Dietary indole-3-carbinol (I3C) has clinical benefits for both cervical cancer and laryngeal papillomatosis, and causes apoptosis of breast cancer cells in vitro. We asked whether I3C and its major acid-catalyzed condensation product diindolylmethane (DIM), which is produced in the stomach after consumption of cruciferous vegetables, could induce apoptosis of cervical cancer cell lines. We also asked whether this effect could be observed in vivo. In vitro, both I3C and DIM caused accumulation of DNA strand breaks in three cervical cancer cell lines. Induction of apoptosis was confirmed by nuclear morphology, nucleosome leakage, altered cytoplasmic membrane permeability and caspase 3 activation. Neither I3C nor DIM caused apoptotic changes in normal human keratinocytes. In C33A cervical cancer cells, DIM was more potent than I3C [dose at which the number of viable cells was 50% of that in untreated cultures (LD(50)) = 50-60 micromol/L for DIM and 200 micromol/L for I3C in a mitochondrial function assay] and faster acting. Furthermore, I3C reduced Bcl-2 protein in a time- and dose-dependent manner. In HPV16-transgenic mice, which develop cervical cancer after chronic estradiol exposure, apoptotic cells were detected in cervical epithelium by TdT-mediated dUTP nick-end labeling staining and by immunohistochemical staining of active caspase 3 only in mice exposed to 17beta-estradiol (E2) and fed I3C. Rare apoptotic cells were also observed by hematoxylin and eosin staining in the spinous layer of the cervical epithelium in both control and transgenic mice. Estradiol reduced the percentage of these late-stage apoptotic cells in the cervical epithelium of transgenic, E2-treated mice, but this reduction was prevented by I3C. These data confirm the proapoptotic action of I3C on transformed cells in vitro, extend the observations to cervical cancer cells and to DIM and show for the first time that dietary I3C results in increased apoptosis in target tissues in vivo.

Links

Publisher Full Text

Authors+Show Affiliations

Chen DZ
North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA.
Qi M
No affiliation info available
Auborn KJ
No affiliation info available
Carter TH
No affiliation info available

MeSH

AnimalsAnticarcinogenic AgentsApoptosisBlotting, WesternCaspase 3CaspasesDNA FragmentationEpitheliumEstradiolFemaleHumansImmunohistochemistryIn Situ Nick-End LabelingIndolesMiceMice, TransgenicPapillomaviridaePrecancerous ConditionsProto-Oncogene Proteins c-bcl-2Tumor Cells, CulturedUterine Cervical Neoplasms

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11739883

Clinical Trial Links

3,3'-Diindolylmethane in Patients With Systemic Lupus Erythematosus

Citation

Chen, D Z., et al. "Indole-3-carbinol and Diindolylmethane Induce Apoptosis of Human Cervical Cancer Cells and in Murine HPV16-transgenic Preneoplastic Cervical Epithelium." The Journal of Nutrition, vol. 131, no. 12, 2001, pp. 3294-302.
Chen DZ, Qi M, Auborn KJ, et al. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr. 2001;131(12):3294-302.
Chen, D. Z., Qi, M., Auborn, K. J., & Carter, T. H. (2001). Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. The Journal of Nutrition, 131(12), 3294-302.
Chen DZ, et al. Indole-3-carbinol and Diindolylmethane Induce Apoptosis of Human Cervical Cancer Cells and in Murine HPV16-transgenic Preneoplastic Cervical Epithelium. J Nutr. 2001;131(12):3294-302. PubMed PMID: 11739883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. AU - Chen,D Z, AU - Qi,M, AU - Auborn,K J, AU - Carter,T H, PY - 2001/12/12/pubmed PY - 2002/1/24/medline PY - 2001/12/12/entrez SP - 3294 EP - 302 JF - The Journal of nutrition JO - J Nutr VL - 131 IS - 12 N2 - Dietary indole-3-carbinol (I3C) has clinical benefits for both cervical cancer and laryngeal papillomatosis, and causes apoptosis of breast cancer cells in vitro. We asked whether I3C and its major acid-catalyzed condensation product diindolylmethane (DIM), which is produced in the stomach after consumption of cruciferous vegetables, could induce apoptosis of cervical cancer cell lines. We also asked whether this effect could be observed in vivo. In vitro, both I3C and DIM caused accumulation of DNA strand breaks in three cervical cancer cell lines. Induction of apoptosis was confirmed by nuclear morphology, nucleosome leakage, altered cytoplasmic membrane permeability and caspase 3 activation. Neither I3C nor DIM caused apoptotic changes in normal human keratinocytes. In C33A cervical cancer cells, DIM was more potent than I3C [dose at which the number of viable cells was 50% of that in untreated cultures (LD(50)) = 50-60 micromol/L for DIM and 200 micromol/L for I3C in a mitochondrial function assay] and faster acting. Furthermore, I3C reduced Bcl-2 protein in a time- and dose-dependent manner. In HPV16-transgenic mice, which develop cervical cancer after chronic estradiol exposure, apoptotic cells were detected in cervical epithelium by TdT-mediated dUTP nick-end labeling staining and by immunohistochemical staining of active caspase 3 only in mice exposed to 17beta-estradiol (E2) and fed I3C. Rare apoptotic cells were also observed by hematoxylin and eosin staining in the spinous layer of the cervical epithelium in both control and transgenic mice. Estradiol reduced the percentage of these late-stage apoptotic cells in the cervical epithelium of transgenic, E2-treated mice, but this reduction was prevented by I3C. These data confirm the proapoptotic action of I3C on transformed cells in vitro, extend the observations to cervical cancer cells and to DIM and show for the first time that dietary I3C results in increased apoptosis in target tissues in vivo. SN - 0022-3166 UR - https://www.unboundmedicine.com/medline/citation/11739883/Indole_3_carbinol_and_diindolylmethane_induce_apoptosis_of_human_cervical_cancer_cells_and_in_murine_HPV16_transgenic_preneoplastic_cervical_epithelium_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.1093/jn/131.12.3294 DB - PRIME DP - Unbound Medicine ER -