دورية أكاديمية
Indole-3-carbinol and its N-alkoxy derivatives preferentially target ERα-positive breast cancer cells.
العنوان: | Indole-3-carbinol and its N-alkoxy derivatives preferentially target ERα-positive breast cancer cells. |
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المؤلفون: | Caruso JA; a Department of Experimental Radiation Oncology ; University of Texas MD Anderson Cancer Center ; Houston , TX USA., Campana R, Wei C, Su CH, Hanks AM, Bornmann WG, Keyomarsi K |
المصدر: | Cell cycle (Georgetown, Tex.) [Cell Cycle] 2014; Vol. 13 (16), pp. 2587-99. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101137841 Publication Model: Print Cited Medium: Internet ISSN: 1551-4005 (Electronic) Linking ISSN: 15514005 NLM ISO Abbreviation: Cell Cycle Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Georgetown, TX : Landes Bioscience, c2002- |
مواضيع طبية MeSH: | Alcohols/*pharmacology , Antineoplastic Agents/*pharmacology , Breast Neoplasms/*metabolism , Estrogen Receptor alpha/*metabolism , Indoles/*pharmacology , Metabolic Networks and Pathways/*drug effects, Alcohols/chemistry ; Antineoplastic Agents/chemistry ; Apoptosis/drug effects ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin E/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Indoles/chemistry ; Leukocyte Elastase/metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction/drug effects |
مستخلص: | Indole-3-carbinol (I3C) is a natural anti-carcinogenic compound found at high concentrations in Brassica vegetables. I3C was recently reported to inhibit neutrophil elastase (NE) activity, while consequently limiting the proteolytic processing of full length cyclin E into pro-tumorigenic low molecular weight cyclin E (LMW-E). In this study, we hypothesized that inhibition of NE activity and resultant LMW-E generation is critical to the anti-tumor effects of I3C. LMW-E was predominately expressed by ERα-negative breast cancer cell lines. However, ERα-positive cell lines demonstrated the greatest sensitivity to the anti-tumor effects of I3C and its more potent N-alkoxy derivatives. We found that I3C was incapable of inhibiting NE activity or the generation of LMW-E. Therefore, this pathway did not contribute to the anti-tumor activity of I3C. Gene expression analyzes identified ligand-activated aryl hydrocarbon receptor (AhR), which mediated sensitivity to the anti-tumor effects of I3C in ERα-positive MCF-7 cells. In this model system, the reactive oxygen species (ROS)-induced upregulation of ATF-3 and pro-apoptotic BH3-only proteins (e.g. NOXA) contributed to the sensitivity of ERα-positive breast cancer cells to the anti-tumor effects of I3C. Overexpression of ERα in MDA-MB-231 cells, which normally lack ERα expression, increased sensitivity to the anti-tumor effects of I3C, demonstrating a direct role for ERα in mediating the sensitivity of breast cancer cell lines to I3C. Our results suggest that ERα signaling amplified the pro-apoptotic effect of I3C-induced AhR signaling in luminal breast cancer cell lines, which was mediated in part through oxidative stress induced upregulation of ATF-3 and downstream BH3-only proteins. |
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معلومات مُعتمدة: | P30 CA016672 United States CA NCI NIH HHS; R01 CA087548 United States CA NCI NIH HHS; R01 CA152228 United States CA NCI NIH HHS; T32 CA163185 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: AhR, aryl hydrocarbon receptor; CYP, cytochrome p450 oxidases; DIM, 3,3-diindoylmethane; ERα, estrogen receptor α; HMECs, human mammary epithelial cells; I3C, indole-3-carbinol; LMW-E, low molecular weight cyclin E; NE, neutrophil elastase; ROS, reactive oxygen species; RPPA, reverse phase protein array; TNBC, triple-receptor negative breast cancer; aryl hydrocarbon receptor; estrogen receptor α; indole-3-carbinol; neutrophil elastase |
المشرفين على المادة: | 0 (Alcohols) 0 (Antineoplastic Agents) 0 (Cyclin E) 0 (ESR1 protein, human) 0 (Estrogen Receptor alpha) 0 (Indoles) 0 (Receptors, Aryl Hydrocarbon) 0 (alkoxyl radical) C11E72455F (indole-3-carbinol) EC 3.4.21.37 (Leukocyte Elastase) |
تواريخ الأحداث: | Date Created: 20141209 Date Completed: 20150819 Latest Revision: 20210816 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC4614451 |
DOI: | 10.4161/15384101.2015.942210 |
PMID: | 25486199 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1551-4005 |
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DOI: | 10.4161/15384101.2015.942210 |