A Caruso, Joseph Campana, Rody Wei, Caimiao Su, Chun-Hui M Hanks, Amanda G Bornmann, William Keyomarsi, Khandan Indole-3-carbinol and its N-alkoxy derivatives preferentially target ER<b>α</b>-positive breast cancer cells <div><p>Indole-3-carbinol (I3C) is a natural anti-carcinogenic compound found at high concentrations in <i>Brassica</i> 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.</p></div> bh;luminal breast cancer cell lines;length cyclin E;sensitivity;ros;er;noxa;Reactive oxygen species;atf;3C Gene expression;breast cancer cell lines;weight cyclin E;NE activity;mcf 2015-10-09
    https://tandf.figshare.com/articles/dataset/Indole_3_carbinol_and_its_N_alkoxy_derivatives_preferentially_target_ER_b_945_b_positive_breast_cancer_cells/1246743
10.6084/m9.figshare.1246743.v2