Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact
Breast cancer is the most prevalent neoplasia among women worldwide. For the estrogen receptor-positive (ER+) phenotype, tamoxifen is the standard hormonal therapy; however, it carries the risk of promoting endometrial carcinoma. Hence, we aimed to evaluate the antiproliferative effect of the phytoc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1576 |
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| author | Rafael Vargas-Castro Rocío García-Becerra Lorenza Díaz Euclides Avila David Ordaz-Rosado Samantha V. Bernadez-Vallejo Saúl Cano-Colín Javier Camacho Fernando Larrea Janice García-Quiroz |
| author_facet | Rafael Vargas-Castro Rocío García-Becerra Lorenza Díaz Euclides Avila David Ordaz-Rosado Samantha V. Bernadez-Vallejo Saúl Cano-Colín Javier Camacho Fernando Larrea Janice García-Quiroz |
| author_sort | Rafael Vargas-Castro |
| collection | DOAJ |
| description | Breast cancer is the most prevalent neoplasia among women worldwide. For the estrogen receptor-positive (ER+) phenotype, tamoxifen is the standard hormonal therapy; however, it carries the risk of promoting endometrial carcinoma. Hence, we aimed to evaluate the antiproliferative effect of the phytochemical α-mangostin (AM) as a co-adjuvant alongside tamoxifen on breast cancer cells to improve its efficacy while reducing its adverse effects on endometrium. For this, ER+ breast cancer cells (MCF-7 and T-47D) and endometrial cells (N30) were treated with AM, 4-hydroxytamoxifen (4-OH-TMX), and their combination. Cell proliferation was evaluated using sulforhodamine B assay, and the pharmacological interaction was determined through the combination index and the dose reduction index calculation. The genes <i>KCNH1</i>, <i>CCDN1, MKI67</i>, and <i>BIRC5</i> were amplified by real-time PCR as indicators of oncogenesis, cell cycle progression, cell proliferation, and apoptosis, respectively. Additionally, genes involved in ER signaling were analyzed. In breast cancer cells, the combination of AM with 4-OH-TMX showed a synergistic antiproliferative effect and favorable dose reduction. AM and 4-OH-TMX decreased <i>KCNH1</i>, <i>CCND1</i>, and <i>BIRC5</i> gene expression. In endometrial cells, AM decreased <i>MKI-67</i> gene expression, while it reverted the 4-OH-TMX-dependent <i>CCND1</i> upregulation. This study establishes the benefits of incorporating AM as a co-adjuvant for first-line ER+ breast cancer therapy. |
| first_indexed | 2024-03-09T16:32:19Z |
| format | Article |
| id | doaj.art-6e53ee82b9064603ab75466329b41d13 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:19Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6e53ee82b9064603ab75466329b41d132023-11-24T15:00:20ZengMDPI AGPharmaceuticals1424-82472023-11-011611157610.3390/ph16111576Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial ImpactRafael Vargas-Castro0Rocío García-Becerra1Lorenza Díaz2Euclides Avila3David Ordaz-Rosado4Samantha V. Bernadez-Vallejo5Saúl Cano-Colín6Javier Camacho7Fernando Larrea8Janice García-Quiroz9Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, MexicoDepartamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N., Ciudad de Mexico 07360, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoDepartamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico 14080, MexicoBreast cancer is the most prevalent neoplasia among women worldwide. For the estrogen receptor-positive (ER+) phenotype, tamoxifen is the standard hormonal therapy; however, it carries the risk of promoting endometrial carcinoma. Hence, we aimed to evaluate the antiproliferative effect of the phytochemical α-mangostin (AM) as a co-adjuvant alongside tamoxifen on breast cancer cells to improve its efficacy while reducing its adverse effects on endometrium. For this, ER+ breast cancer cells (MCF-7 and T-47D) and endometrial cells (N30) were treated with AM, 4-hydroxytamoxifen (4-OH-TMX), and their combination. Cell proliferation was evaluated using sulforhodamine B assay, and the pharmacological interaction was determined through the combination index and the dose reduction index calculation. The genes <i>KCNH1</i>, <i>CCDN1, MKI67</i>, and <i>BIRC5</i> were amplified by real-time PCR as indicators of oncogenesis, cell cycle progression, cell proliferation, and apoptosis, respectively. Additionally, genes involved in ER signaling were analyzed. In breast cancer cells, the combination of AM with 4-OH-TMX showed a synergistic antiproliferative effect and favorable dose reduction. AM and 4-OH-TMX decreased <i>KCNH1</i>, <i>CCND1</i>, and <i>BIRC5</i> gene expression. In endometrial cells, AM decreased <i>MKI-67</i> gene expression, while it reverted the 4-OH-TMX-dependent <i>CCND1</i> upregulation. This study establishes the benefits of incorporating AM as a co-adjuvant for first-line ER+ breast cancer therapy.https://www.mdpi.com/1424-8247/16/11/1576α-mangostinbreast cancertamoxifencombination indexsynergismendometrium cells |
| spellingShingle | Rafael Vargas-Castro Rocío García-Becerra Lorenza Díaz Euclides Avila David Ordaz-Rosado Samantha V. Bernadez-Vallejo Saúl Cano-Colín Javier Camacho Fernando Larrea Janice García-Quiroz Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact Pharmaceuticals α-mangostin breast cancer tamoxifen combination index synergism endometrium cells |
| title | Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact |
| title_full | Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact |
| title_fullStr | Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact |
| title_full_unstemmed | Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact |
| title_short | Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact |
| title_sort | enhancing tamoxifen therapy with α mangostin synergistic antiproliferative effects on breast cancer cells and potential reduced endometrial impact |
| topic | α-mangostin breast cancer tamoxifen combination index synergism endometrium cells |
| url | https://www.mdpi.com/1424-8247/16/11/1576 |
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