Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling
Approximately 80% of breast cancer (BC) cases express the estrogen receptor (ER), and 30–40% of these cases acquire resistance to endocrine therapies over time. Hyperactivation of Akt is one of the mechanisms by which endocrine resistance is acquired. Apigenin (Api), a flavone found in several plant...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/470 |
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| author | Thu Ha Pham Yann Le Page Frédéric Percevault François Ferrière Gilles Flouriot Farzad Pakdel |
| author_facet | Thu Ha Pham Yann Le Page Frédéric Percevault François Ferrière Gilles Flouriot Farzad Pakdel |
| author_sort | Thu Ha Pham |
| collection | DOAJ |
| description | Approximately 80% of breast cancer (BC) cases express the estrogen receptor (ER), and 30–40% of these cases acquire resistance to endocrine therapies over time. Hyperactivation of Akt is one of the mechanisms by which endocrine resistance is acquired. Apigenin (Api), a flavone found in several plant foods, has shown beneficial effects in cancer and chronic diseases. Here, we studied the therapeutic potential of Api in the treatment of ER-positive, endocrine therapy-resistant BC. To achieve this objective, we stably overexpressed the constitutively active form of the Akt protein in MCF-7 cells (named the MCF-7/Akt clone). The proliferation of MCF-7/Akt cells is partially independent of estradiol (E2) and exhibits an incomplete response to the anti-estrogen agent 4-hydroxytamoxifen, demonstrating the resistance of these cells to hormone therapy. Api exerts an antiproliferative effect on the MCF-7/Akt clone. Api inhibits the proliferative effect of E2 by inducing G2/M phase cell cycle arrest and apoptosis. Importantly, Api inhibits the Akt/FOXM1 signaling pathway by decreasing the expression of FOXM1, a key transcription factor involved in the cell cycle. Api also alters the expression of genes regulated by FOXM1, including cell cycle-related genes, particularly in the MCF-7/Akt clone. Together, our results strengthen the therapeutic potential of Api for the treatment of endocrine-resistant BC. |
| first_indexed | 2024-03-10T13:28:26Z |
| format | Article |
| id | doaj.art-cf183ad118b543ffb6046cc3c5e92c3c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:28:26Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cf183ad118b543ffb6046cc3c5e92c3c2023-11-21T08:36:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122147010.3390/ijms22010470Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 SignalingThu Ha Pham0Yann Le Page1Frédéric Percevault2François Ferrière3Gilles Flouriot4Farzad Pakdel5Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceInserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceInserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceInserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceInserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceInserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, FranceApproximately 80% of breast cancer (BC) cases express the estrogen receptor (ER), and 30–40% of these cases acquire resistance to endocrine therapies over time. Hyperactivation of Akt is one of the mechanisms by which endocrine resistance is acquired. Apigenin (Api), a flavone found in several plant foods, has shown beneficial effects in cancer and chronic diseases. Here, we studied the therapeutic potential of Api in the treatment of ER-positive, endocrine therapy-resistant BC. To achieve this objective, we stably overexpressed the constitutively active form of the Akt protein in MCF-7 cells (named the MCF-7/Akt clone). The proliferation of MCF-7/Akt cells is partially independent of estradiol (E2) and exhibits an incomplete response to the anti-estrogen agent 4-hydroxytamoxifen, demonstrating the resistance of these cells to hormone therapy. Api exerts an antiproliferative effect on the MCF-7/Akt clone. Api inhibits the proliferative effect of E2 by inducing G2/M phase cell cycle arrest and apoptosis. Importantly, Api inhibits the Akt/FOXM1 signaling pathway by decreasing the expression of FOXM1, a key transcription factor involved in the cell cycle. Api also alters the expression of genes regulated by FOXM1, including cell cycle-related genes, particularly in the MCF-7/Akt clone. Together, our results strengthen the therapeutic potential of Api for the treatment of endocrine-resistant BC.https://www.mdpi.com/1422-0067/22/1/470breast cancerendocrine resistanceERAktFOXM1phytochemicals |
| spellingShingle | Thu Ha Pham Yann Le Page Frédéric Percevault François Ferrière Gilles Flouriot Farzad Pakdel Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling International Journal of Molecular Sciences breast cancer endocrine resistance ER Akt FOXM1 phytochemicals |
| title | Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling |
| title_full | Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling |
| title_fullStr | Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling |
| title_full_unstemmed | Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling |
| title_short | Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling |
| title_sort | apigenin a partial antagonist of the estrogen receptor er inhibits er positive breast cancer cell proliferation through akt foxm1 signaling |
| topic | breast cancer endocrine resistance ER Akt FOXM1 phytochemicals |
| url | https://www.mdpi.com/1422-0067/22/1/470 |
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