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Updated: Mar 28, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1
Patrick P Carriere1, Shawn D Llopis2, Anna C Naiki3
1College of Pharmacy, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA. pcarriere@msm.edu.
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.
Insights
Glyceollin I reverses drug resistance in breast cancer by targeting epithelial mesenchymal transition (EMT). This phytoalexin reduces cancer cell invasion and migration, offering potential for new breast cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aromatase inhibitors are standard endocrine therapy for estrogen-dependent breast cancer.
- Drug resistance limits the efficacy of aromatase inhibitors, necessitating novel therapeutic strategies.
- Epithelial mesenchymal transition (EMT) is implicated in letrozole resistance and enhanced cancer cell motility.
Purpose of the Study:
- To investigate the therapeutic potential of glyceollin I in overcoming letrozole resistance in breast cancer.
- To elucidate the role of glyceollin I in modulating EMT markers and cellular behavior in resistant breast cancer cells.
Main Methods:
- Treatment of letrozole-resistant breast cancer cells (LTLT-Ca) with glyceollin I.
- Analysis of epithelial mesenchymal transition (EMT) markers, including Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and E-cadherin.
- Assessment of cell proliferation, invasion, and migration in vitro.
- In vivo studies in ovariectomized, female nude mice to evaluate tumor characteristics.
Main Results:
- Glyceollin I treatment restored epithelial characteristics and decreased proliferation in LTLT-Ca cells.
- Glyceollin I significantly reduced ZEB1 expression and increased E-cadherin expression.
- In vivo, glyceollin I treatment led to decreased ZEB1 and N-cadherin, and increased E-cadherin in tumors.
- Glyceollin I inhibited invasion by 68% and migration by 83% in LTLT-Ca cells.
Conclusions:
- Glyceollin I effectively targets epithelial mesenchymal transition (EMT) in letrozole-resistant breast cancer.
- Glyceollin I demonstrates therapeutic potential by reversing drug resistance and inhibiting cancer cell motility.
- Further investigation of glyceollin I as a therapeutic agent for resistant breast cancer is warranted.
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