Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis
Abstract
:1. Introduction
2. Results
2.1. Letrozole-Resistant T47D Cells Are Codependent on Hormone and Growth Factor Signaling Cascades
2.2. Estrogen-Dependent Letrozole-Resistant Cells Are Non-Migratory
2.3. Glyceollin and Lapatinib Treatment Inhibits Proliferation of Letrozole-Resistant Breast Cancer Cells
2.4. Glyceollin and Lapatinib Dramatically Inhibit Survival of Letrozole-Resistant Breast Cancer Cells
2.5. Glyceollin and Lapatinib Induce Cell Cycle Arrest in Letrozole-Resistant Breast Cancer Cells
2.6. Glyceollin Induces Apoptosis in Letrozole-Sensitive and Letrozole-Resistant Breast Cancer Cells
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Viability Assay
4.3. Colony Formation Assay
4.4. Migration Assay
4.5. Flow Cytometry
4.6. Caspase 3/7 Apoptosis Assay
4.7. Gel Electrophoresis and Western Blot Analysis
4.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Disclaimer
Abbreviations
AI | aromatase inhibitors |
Ca2+ | calcium ion |
CO2 | carbon dioxide |
DMSO | dimethyl sulfoxide |
EGFR | epidermal growth factor receptor |
ER- | estrogen receptor negative |
ER+ | estrogen receptor positive |
EMT | epithelial-to-mesenchymal-transition |
FBS | fetal bovine serum |
FDA | Federal Drug Administration |
HER2 | human epidermal growth factor receptor |
HR+ | hormone receptor positive |
LTED | long-term estrogen-deprived |
LTLT-Ca | long-term letrozole-treated |
MAPK | mitogen-activated protein kinase |
Mg2+ | magnesium ion |
PBS | phosphate-buffered saline |
PI | propidium iodine |
PR+ | progesterone receptor positive |
RPM | revolutions per minute |
T47Darom | T47Daromatase-overexpressing cells |
T47DaromLR | T47D-aromatase-overexpressing letrozole-resistant cells |
Appendix A
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Cell Line | G0/G1 | S | G2/M | Total Number of Cells |
---|---|---|---|---|
T47Darom | ||||
Control | 70.00% (8413) | 11.60% (1392) | 12.90% (1553) | 11358 |
Lapatinib | 74.80% (7231) | 8.10% (783) | 12.50% (1212) | 9226 |
Glyceollin | 72.30% (6363) | 8.10% (709) | 13.70% (1210) | 8282 |
Lapatinib + Glyceollin | 66.20% (5850) | 6.80% (604) | 14.30% (1266) | 7720 |
T47DaromLR | ||||
Control | 75.55% (5857) | 10.05% (779) | 13.85% (1074) | 7753 |
Lapatinib | 79.85% (5828) | 7.65% (560) | 11.60% (850) | 7323 |
Glyceollin | 75.85% (6084) | 8.8% (706) | 7.3% (8585) | 8021 |
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Walker, 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. Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis. Int. J. Mol. Sci. 2022, 23, 2887. https://doi.org/10.3390/ijms23052887
Walker RR, Patel JR, Gupta A, Davidson AM, Williams CC, Payton-Stewart F, Boué SM, Burow ME, Khupse R, Tilghman SL. Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis. International Journal of Molecular Sciences. 2022; 23(5):2887. https://doi.org/10.3390/ijms23052887
Chicago/Turabian StyleWalker, Rashidra R., Jankiben R. Patel, Akash Gupta, A. Michael Davidson, Christopher C. Williams, Florastina Payton-Stewart, Stephen M. Boué, Matthew E. Burow, Rahul Khupse, and Syreeta L. Tilghman. 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 23, no. 5: 2887. https://doi.org/10.3390/ijms23052887