α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells

Galia Lara-Sotelo; Lorenza Díaz; Rocío García-Becerra; Euclides Avila; Heriberto Prado-Garcia; Gabriela Morales-Guadarrama; María de Jesús Ibarra-Sánchez; José Esparza-López; Fernando Larrea; Janice García-Quiroz

LAPSE

Living Archive for Process Systems Engineering

LAPSE:2023.24725

Published Article

LAPSE:2023.24725

α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells

Galia Lara-Sotelo, Lorenza Díaz, Rocío García-Becerra, Euclides Avila, Heriberto Prado-Garcia, Gabriela Morales-Guadarrama, María de Jesús Ibarra-Sánchez, José Esparza-López, Fernando Larrea, Janice García-Quiroz

March 28, 2023

Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering 5-fluorouracil drawbacks, without affecting its therapeutic efficacy by the concomitant use with natural products. Herein, we aimed at evaluating whether α-mangostin, a natural antineoplastic compound, could increase the anticancer effect of 5-fluorouracil in different breast cancer cell lines, allowing for dose reduction. Cell proliferation was evaluated by sulforhodamine-B assays, inhibitory concentrations and potency were calculated by dose-response curves, followed by analysis of their pharmacological interaction by the combination-index method and dose-reduction index. Cell cycle distribution was evaluated by flow cytometry. Each compound inhibited cell proliferation in a dose-dependent manner, the triple negative breast cancer cells being the most sensitive. When 5-fluorouracil and α-mangostin were used concomitantly, synergistic antiproliferative effect was observed. The calculated dose-reduction index suggested that this combination exhibits therapeutic potential for reducing 5-fluorouracil dosage in breast cancer. Mechanistically, the cotreatment induced cell death in a greater extent than each drug alone. Therefore, α-mangostin could be used as a potent co-adjuvant for 5-fluorouracil in breast cancer.

Record ID

LAPSE:2023.24725

Keywords

5-fluorouracil, breast cancer, combination index, dose-reduction index, α-mangostin

Subject

Biosystems

Suggested Citation

Lara-Sotelo G, Díaz L, García-Becerra R, Avila E, Prado-Garcia H, Morales-Guadarrama G, Ibarra-Sánchez MDJ, Esparza-López J, Larrea F, García-Quiroz J. α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells. (2023). LAPSE:2023.24725

Author Affiliations

Lara-Sotelo G: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico
Díaz L: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico [ORCID]
García-Becerra R: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
Avila E: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico
Prado-Garcia H: Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México 14080, Mexico [ORCID]
Morales-Guadarrama G: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico
Ibarra-Sánchez MDJ: Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico [ORCID]
Esparza-López J: Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico
Larrea F: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico
García-Quiroz J: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico

Journal Name

Processes

Volume

9

Issue

3

First Page

458

Year

2021

Publication Date

2021-03-03