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

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, KiTani Parker-Lemieux, Florastina Payton-Stewart, Christopher C. Williams, Stephen M. Boué, Matthew E. Burow, Bridgette Collins-Burow, Aaron Hilliard, A. Michael Davidson and Syreeta L. Tilghman
Additional contact information
Patrick P. Carriere: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
Shawn D. Llopis: College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
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

IJERPH, 2015, vol. 13, issue 1, 1-17

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.

Keywords: letrozole resistance; epithelial mesenchymal transition; breast cancer; phytochemicals; aromatase inhibitors; metastasis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2015
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