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Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-res...

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Autores principales: Walker, Rashidra R., Patel, Jankiben R., Gupta, Akash, Davidson, A. Michael, Williams, Christopher C., Payton-Stewart, Florastina, Boué, Stephen M., Burow, Matthew E., Khupse, Rahul, Tilghman, Syreeta L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911299/
https://www.ncbi.nlm.nih.gov/pubmed/35270029
http://dx.doi.org/10.3390/ijms23052887
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author Walker, Rashidra R.
Patel, Jankiben R.
Gupta, Akash
Davidson, A. Michael
Williams, Christopher C.
Payton-Stewart, Florastina
Boué, Stephen M.
Burow, Matthew E.
Khupse, Rahul
Tilghman, Syreeta L.
author_facet Walker, Rashidra R.
Patel, Jankiben R.
Gupta, Akash
Davidson, A. Michael
Williams, Christopher C.
Payton-Stewart, Florastina
Boué, Stephen M.
Burow, Matthew E.
Khupse, Rahul
Tilghman, Syreeta L.
author_sort Walker, Rashidra R.
collection PubMed
description Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors.
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spelling pubmed-89112992022-03-11 Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis Walker, Rashidra R. Patel, Jankiben R. Gupta, Akash Davidson, A. Michael Williams, Christopher C. Payton-Stewart, Florastina Boué, Stephen M. Burow, Matthew E. Khupse, Rahul Tilghman, Syreeta L. Int J Mol Sci Article Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors. MDPI 2022-03-07 /pmc/articles/PMC8911299/ /pubmed/35270029 http://dx.doi.org/10.3390/ijms23052887 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Walker, Rashidra R.
Patel, Jankiben R.
Gupta, Akash
Davidson, A. Michael
Williams, Christopher C.
Payton-Stewart, Florastina
Boué, Stephen M.
Burow, Matthew E.
Khupse, Rahul
Tilghman, Syreeta L.
Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title_full Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title_fullStr Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title_full_unstemmed Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title_short Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
title_sort glyceollins trigger anti-proliferative effects in hormone-dependent aromatase-inhibitor-resistant breast cancer cells through the induction of apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911299/
https://www.ncbi.nlm.nih.gov/pubmed/35270029
http://dx.doi.org/10.3390/ijms23052887
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