Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
AffiliationDepartment of Medicine, University of Arizona
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CitationWalker, R. R., Patel, J. R., Gupta, A., Davidson, A. M., Williams, C. C., Payton-Stewart, F., Boué, S. M., Burow, M. E., Khupse, R., & Tilghman, S. L. (2022). Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis. International Journal of Molecular Sciences.
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AbstractAromatase 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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Except where otherwise noted, this item's license is described as Copyright © 2022 by the authors. 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/).
- Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.
- Authors: Gupta A, Mehta R, Alimirah F, Peng X, Murillo G, Wiehle R, Mehta RG
- Issue date: 2013 Jan
- The aromatase inhibitor letrozole and inhibitors of insulin-like growth factor I receptor synergistically induce apoptosis in in vitro models of estrogen-dependent breast cancer.
- Authors: Lisztwan J, Pornon A, Chen B, Chen S, Evans DB
- Issue date: 2008
- Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade.
- Authors: Walker RR, Gallegos KM, Bratton MR, Lemieux KP, Zhang K, Wang G, Davidson AM, Tilghman SL
- Issue date: 2021 Feb
- Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.
- Authors: Carriere PP, Llopis SD, Naiki AC, Nguyen G, Phan T, Nguyen MM, Preyan LC, Yearby L, Pratt J, Burks H, Davenport IR, Nguyen TA, Parker-Lemieux K, Payton-Stewart F, Williams CC, Boué SM, Burow ME, Collins-Burow B, Hilliard A, Davidson AM, Tilghman SL
- Issue date: 2015 Dec 22
- The importance of HER2 signaling in the tumor-initiating cell population in aromatase inhibitor-resistant breast cancer.
- Authors: Gilani RA, Kazi AA, Shah P, Schech AJ, Chumsri S, Sabnis G, Jaiswal AK, Brodie AH
- Issue date: 2012 Oct