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

International Journal of Environmental Research and Public Health

Patrick P. Carriere²  Shawn D. Llopis²  Anna C. Naiki²  Gina Nguyen²  Tina Phan²  Mary M. Nguyen²  Lynez C. Preyan²  Letitia Yearby²  Jamal Pratt²  Hope Burks⁶  Ian R. Davenport¹  Thu A. Nguyen²  KiTani Parker-Lemieux²  Florastina Payton-Stewart³  Christopher C. Williams²  Stephen M. Boué⁵  Matthew E. Burow⁶  Bridgette Collins-Burow⁶  Aaron Hilliard⁷  A. Michael Davidson⁷  Syreeta L. Tilghman⁷  Mark Edberg⁴  Barbara E. Hayes⁴  Valerie Montgomery Rice⁴ 

[1] Division of Biological and Public Health Sciences, College of Arts and Sciences, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;Division of Mathematical and Physical Sciences, College of Arts and Sciences, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;;College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USASouthern Regional Research Center, United States Department of Agriculture, New Orleans, LA 70124, USA;Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA;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;

关键词: letrozole resistance;    epithelial mesenchymal transition;    breast cancer;    phytochemicals;    aromatase inhibitors;    metastasis;   

DOI  :  10.3390/ijerph13010010

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.