Skip to main content
ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #312102
Title: Glyceollin I reverses epithelial to mesenchymal transition in letrozole resistance

Author
item CARRIERE, PATRICK - Xavier University
item LLOPIS, SHAWN - Xavier University
item NAIKI, ANNA - Xavier University
item NGUYEN, GINA - Xavier University
item PHAN, TINA - Xavier University
item NGUYEN, MARY - Xavier University
item PREYAN, LYNEZ - Xavier University
item YEARBY, LETECIA - Xavier University
item Boue, Stephen
item TILGHMAN, SYREETA - Xavier University

Submitted to: International Journal of Environmental Research and Public Health
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/24/2015
Publication Date: 12/22/2015
Citation: Carriere, P., Llopis, S., Naiki, A., Nguyen, G., Phan, T., Nguyen, M., Preyan, L., Yearby, L., Boue, S.M., Tilghman, S. 2015. Glyceollin I reverses epithelial to mesenchymal transition in letrozole resistance. International Journal of Environmental Research and Public Health. 13:10.

Interpretive Summary: Although pharmaceutical agents to treat breast cancer, such as letrozole; are standard endocrine therapy for postmenopausal women with early stage metastatic estrogen-dependent breast cancer, the major limitation in managing this disease is the development of drug resistance; therefore, a better understanding of this process is critical towards developing novel strategies and therapies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance that was associated with hormone independence and enhanced cell activity. Letrozole-resistant breast cancer cells were treated with a novel soy compound, glyceollin I, and biological and functional studies were performed. Glyceollin I-treated cells exhibited a decrease in cell viability and proliferation. Letrozole resistance caused an increase in gene expression related to metastasis, while glyceollin I treatment caused a reduction. In vivo studies were performed on postmenopausal female nude mice, and results indicated that glyceollin treated tumors demonstrated potential for decreased metastasis. We demonstrated for the first time, the potential of a novel soy compound, glyceollin I, to the potential for metastasis in letrozole resistant breast cancer cells, which may aid in the development of novel anticancer pharmaceutical agents.

Technical Abstract: Although aromatase inhibitors, such as letrozole; are standard endocrine therapy for postmenopausal women with early stage metastatic estrogen-dependent breast cancer, the major limitation in managing this disease is the development of drug resistance; therefore, a better understanding of this process is critical towards developing novel strategies and therapies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance that was associated with hormone independence, and enhanced cell motility implicating the involvement of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and biological and functional studies were performed. Glyceollin I-treated LTLT-Ca cells exhibited morphological characteristics synonymous with an epithelial phenotype independent of ERalpha, and a 72.9% and 57.7% decrease in cell viability and proliferation, respectively. Letrozole resistance caused a 4.51-fold increase in ZEB1 expression, while glyceollin I treatment caused a 3.39-fold reduction. Immunofluorescence analyses indicated a glyceollin I-induced increase in E-cadherin protein expression. In vivo studies were performed on postmenopausal female nude mice, and results indicated that glyceollin treated tumors were weakly stained for ZEB1 and N-cadherin while strongly stained for E-cadherin. When compared to letrozole sensitive cells, LTLT-Ca cells display enhanced motility;however, in the presence of glyceollin I, there is a 68% and 83% decrease in invasion and migration, respectively. We demonstrated for the first time, the potential of a novel phytoalexin, glyceollin I, to reverse EMT in letrozole resistant breast cancer cells, which may aid in the development of novel EMT inhibitors.