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Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

Author

Listed:
  • Patrick P. Carriere

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
    These authors contributed equally to this work.)

  • Shawn D. Llopis

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
    These authors contributed equally to this work.)

  • Anna C. Naiki

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Gina Nguyen

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Tina Phan

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Mary M. Nguyen

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Lynez C. Preyan

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Letitia Yearby

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Jamal Pratt

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Hope Burks

    (Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA)

  • Ian R. Davenport

    (Division of Biological and Public Health Sciences, College of Arts and Sciences, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Thu A. Nguyen

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • KiTani Parker-Lemieux

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Florastina Payton-Stewart

    (Division of Mathematical and Physical Sciences, College of Arts and Sciences, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Christopher C. Williams

    (College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA)

  • Stephen M. Boué

    (Southern Regional Research Center, United States Department of Agriculture, New Orleans, LA 70124, USA)

  • Matthew E. Burow

    (Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA)

  • Bridgette Collins-Burow

    (Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA)

  • Aaron Hilliard

    (Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307, USA)

  • A. Michael Davidson

    (Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307, USA)

  • Syreeta L. Tilghman

    (Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307, USA)

Abstract

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

Suggested Citation

  • Patrick P. Carriere & Shawn D. Llopis & Anna C. Naiki & Gina Nguyen & Tina Phan & Mary M. Nguyen & Lynez C. Preyan & Letitia Yearby & Jamal Pratt & Hope Burks & Ian R. Davenport & Thu A. Nguyen & KiTa, 2015. "Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1," IJERPH, MDPI, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:gam:jijerp:v:13:y:2015:i:1:p:10-:d:60997
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