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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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Autores principales: Vargas-Castro, Rafael, García-Becerra, Rocío, Díaz, Lorenza, Avila, Euclides, Ordaz-Rosado, David, Bernadez-Vallejo, Samantha V., Cano-Colín, Saúl, Camacho, Javier, Larrea, Fernando, García-Quiroz, Janice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675669/
https://www.ncbi.nlm.nih.gov/pubmed/38004441
http://dx.doi.org/10.3390/ph16111576
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author Vargas-Castro, Rafael
García-Becerra, Rocío
Díaz, Lorenza
Avila, Euclides
Ordaz-Rosado, David
Bernadez-Vallejo, Samantha V.
Cano-Colín, Saúl
Camacho, Javier
Larrea, Fernando
García-Quiroz, Janice
author_facet Vargas-Castro, Rafael
García-Becerra, Rocío
Díaz, Lorenza
Avila, Euclides
Ordaz-Rosado, David
Bernadez-Vallejo, Samantha V.
Cano-Colín, Saúl
Camacho, Javier
Larrea, Fernando
García-Quiroz, Janice
author_sort Vargas-Castro, Rafael
collection PubMed
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 KCNH1, CCDN1, MKI67, and BIRC5 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 KCNH1, CCND1, and BIRC5 gene expression. In endometrial cells, AM decreased MKI-67 gene expression, while it reverted the 4-OH-TMX-dependent CCND1 upregulation. This study establishes the benefits of incorporating AM as a co-adjuvant for first-line ER+ breast cancer therapy.
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spelling pubmed-106756692023-11-08 Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact Vargas-Castro, Rafael García-Becerra, Rocío Díaz, Lorenza Avila, Euclides Ordaz-Rosado, David Bernadez-Vallejo, Samantha V. Cano-Colín, Saúl Camacho, Javier Larrea, Fernando García-Quiroz, Janice Pharmaceuticals (Basel) Article 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 KCNH1, CCDN1, MKI67, and BIRC5 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 KCNH1, CCND1, and BIRC5 gene expression. In endometrial cells, AM decreased MKI-67 gene expression, while it reverted the 4-OH-TMX-dependent CCND1 upregulation. This study establishes the benefits of incorporating AM as a co-adjuvant for first-line ER+ breast cancer therapy. MDPI 2023-11-08 /pmc/articles/PMC10675669/ /pubmed/38004441 http://dx.doi.org/10.3390/ph16111576 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Vargas-Castro, Rafael
García-Becerra, Rocío
Díaz, Lorenza
Avila, Euclides
Ordaz-Rosado, David
Bernadez-Vallejo, Samantha V.
Cano-Colín, Saúl
Camacho, Javier
Larrea, Fernando
García-Quiroz, Janice
Enhancing Tamoxifen Therapy with α-Mangostin: Synergistic Antiproliferative Effects on Breast Cancer Cells and Potential Reduced Endometrial Impact
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675669/
https://www.ncbi.nlm.nih.gov/pubmed/38004441
http://dx.doi.org/10.3390/ph16111576
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