Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA)
Selective estrogen receptor modulators (SERMs) are steroid analogs with dual functionality, acting as partial estrogen receptor agonists to preserve postmenopausal bone density and as estrogen receptor antagonists in breast tissue. Bazedoxifene acetate (BZA) is an FDA-approved, third-generation SERM...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/699 |
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| author | Monica Szmyd Aisha Zanib Victoria Behlow Erin Hallman Samantha Pfiffner Raquel Yaldo Nina Prudhomme Katelyn Farrar Sumi Dinda |
| author_facet | Monica Szmyd Aisha Zanib Victoria Behlow Erin Hallman Samantha Pfiffner Raquel Yaldo Nina Prudhomme Katelyn Farrar Sumi Dinda |
| author_sort | Monica Szmyd |
| collection | DOAJ |
| description | Selective estrogen receptor modulators (SERMs) are steroid analogs with dual functionality, acting as partial estrogen receptor agonists to preserve postmenopausal bone density and as estrogen receptor antagonists in breast tissue. Bazedoxifene acetate (BZA) is an FDA-approved, third-generation SERM used in the treatment of osteoporosis in women. It demonstrates potential as a therapeutic option for breast cancer patients undergoing endocrine therapy. Our study aimed to assess BZA’s effects on Estrogen Receptor Alpha (ERα) and tumor suppressor gene BRCA1 in T-47D and MCF-7 breast cancer cells, using Western blots, cellular viability, apoptosis assays, and RT-qPCR. Cells were cultured in 5% charcoal-stripped fetal bovine serum for six days to deplete endogenous steroids. Following a 24 h exposure to 2 µM BZA (optimal concentration determined from 1 nM–2 µM studies), Western blot analyses revealed reduced ERα and BRCA1 protein levels in both cell lines. ERα decreased by 48–63% and BRCA1 by 61–64%, indicating sensitivity to antiestrogens. Cytolocalization of ERα and BRCA1 remained unchanged after BZA and 17-β-estradiol (E<sub>2</sub>) treatment. ESR1 mRNA expression correlated with Western blot findings. Image cytometric analysis using the stain, propidium iodide, detected decreased cellular proliferation in T-47D and MCF-7 cells following a 6-day treatment ranging from 1 nM to 2 µM BZA. BZA treatment alone led to a tenfold reduction in cellular proliferation compared to estrogen-treated cells, suggesting antiproliferative effects. Understanding BZA’s modulation of BRCA1 and ERα, along with their mechanistic interactions, is vital for comprehending its impact on breast cancer tumor suppressors and hormone receptors. |
| first_indexed | 2024-03-07T22:38:56Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:56Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-abd0b2e882a3433c816c76db5cb9b9322024-02-23T15:10:38ZengMDPI AGCancers2072-66942024-02-0116469910.3390/cancers16040699Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA)Monica Szmyd0Aisha Zanib1Victoria Behlow2Erin Hallman3Samantha Pfiffner4Raquel Yaldo5Nina Prudhomme6Katelyn Farrar7Sumi Dinda8Department of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USADepartment of Clinical and Diagnostic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309, USASelective estrogen receptor modulators (SERMs) are steroid analogs with dual functionality, acting as partial estrogen receptor agonists to preserve postmenopausal bone density and as estrogen receptor antagonists in breast tissue. Bazedoxifene acetate (BZA) is an FDA-approved, third-generation SERM used in the treatment of osteoporosis in women. It demonstrates potential as a therapeutic option for breast cancer patients undergoing endocrine therapy. Our study aimed to assess BZA’s effects on Estrogen Receptor Alpha (ERα) and tumor suppressor gene BRCA1 in T-47D and MCF-7 breast cancer cells, using Western blots, cellular viability, apoptosis assays, and RT-qPCR. Cells were cultured in 5% charcoal-stripped fetal bovine serum for six days to deplete endogenous steroids. Following a 24 h exposure to 2 µM BZA (optimal concentration determined from 1 nM–2 µM studies), Western blot analyses revealed reduced ERα and BRCA1 protein levels in both cell lines. ERα decreased by 48–63% and BRCA1 by 61–64%, indicating sensitivity to antiestrogens. Cytolocalization of ERα and BRCA1 remained unchanged after BZA and 17-β-estradiol (E<sub>2</sub>) treatment. ESR1 mRNA expression correlated with Western blot findings. Image cytometric analysis using the stain, propidium iodide, detected decreased cellular proliferation in T-47D and MCF-7 cells following a 6-day treatment ranging from 1 nM to 2 µM BZA. BZA treatment alone led to a tenfold reduction in cellular proliferation compared to estrogen-treated cells, suggesting antiproliferative effects. Understanding BZA’s modulation of BRCA1 and ERα, along with their mechanistic interactions, is vital for comprehending its impact on breast cancer tumor suppressors and hormone receptors.https://www.mdpi.com/2072-6694/16/4/699ERαBRCA1estrogen receptortumor suppressor genebazedoxifene acetatebreast cancer |
| spellingShingle | Monica Szmyd Aisha Zanib Victoria Behlow Erin Hallman Samantha Pfiffner Raquel Yaldo Nina Prudhomme Katelyn Farrar Sumi Dinda Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) Cancers ERα BRCA1 estrogen receptor tumor suppressor gene bazedoxifene acetate breast cancer |
| title | Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) |
| title_full | Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) |
| title_fullStr | Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) |
| title_full_unstemmed | Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) |
| title_short | Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA) |
| title_sort | modulation of estrogen receptor alpha erα and tumor suppressor gene brca1 in breast cancer cells by bazedoxifene acetate bza |
| topic | ERα BRCA1 estrogen receptor tumor suppressor gene bazedoxifene acetate breast cancer |
| url | https://www.mdpi.com/2072-6694/16/4/699 |
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