The Antiproliferative and Pro-apoptotic Role of 2-aminoethyl dihydrogen Phosphate in Triple-negative Breast Tumor Cells

Neto, Antenor Pereira Bonfim; Cabral, Laertty Garcia de Sousa; Oliveira, Thalles Anthony Duarte; Pacheco, Julio Carlstron; Alves, Michele Joana; Hernández, Mercedes Reyes; Laiso, Rosa Andreia Nogueira; Maria, Durvanei Augusto

doi:10.17265/2328-2150/2021.04.005

Cited by 1 publication

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“…The lack of homogeneity in results stimulates further investigation into its synergistic effect associated with 2-AEH2P, especially considering the presented data. The combination of paclitaxel + 2-AEH2P, investigated by our group in triple-negative breast cancer 4T1 cells, increased the antiproliferative potential, exhibiting morphological changes such as cytoplasmic retraction and regression of the cytoskeleton [63]. It also showed additive pharmacological effects that may favor antitumor therapy and attenuate systemic toxicity.…”

Section: Discussionmentioning

confidence: 99%

2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor

Alves,

Cabral,

Totti

et al. 2024

Biomedicines

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The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

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Section: Discussionmentioning

confidence: 99%