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

International Journal of Environmental Research and Public Health

Patrick P. Carriere¹  Jamal Pratt¹  Christopher C. Williams¹  KiTani Parker-Lemieux¹  Shawn D. Llopis¹  Lynez C. Preyan¹  Thu A. Nguyen¹  Tina Phan¹  Letitia Yearby¹  Mary M. Nguyen¹  Gina Nguyen¹  Anna C. Naiki¹  Aaron Hilliard²  Syreeta L. Tilghman²  Ian R. Davenport³  Florastina Payton-Stewart⁴  A. Michael Davidson⁵  Stephen M. Boué⁶  Hope Burks⁷  Matthew E. Burow⁷  Bridgette Collins-Burow⁷ 

[1] College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA;;Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&Division of Biological and Public Health Sciences, College of Arts and Sciences, 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;M University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307, USA;Southern 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;

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

DOI  :  10.3390/ijerph13010010

来源: DOAJ

【 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】

Unknown