| Autor: |
Alves MG; Development and Innovation Laboratory, Butantan Institute, São Paulo 05359-900, Brazil.; Graduate Program in Medical Sciences, College of Medicine, University of São Paulo, São Paulo 05508-220, Brazil., Cabral LGS; Development and Innovation Laboratory, Butantan Institute, São Paulo 05359-900, Brazil.; Graduate Program in Medical Sciences, College of Medicine, University of São Paulo, São Paulo 05508-220, Brazil., Totti PGF; Graduate Program in Structural and Functional Interactions in Rehabilitation, Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil., Azarias FR; Development and Innovation Laboratory, Butantan Institute, São Paulo 05359-900, Brazil., Pomini KT; Graduate Program in Structural and Functional Interactions in Rehabilitation, Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil., Rici REG; Graduate Program in Structural and Functional Interactions in Rehabilitation, Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil.; Graduate Program in Anatomy of Domestic and Wild Animals, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-220, Brazil., Laiso RAN; Development and Innovation Laboratory, Butantan Institute, São Paulo 05359-900, Brazil., Maria DA; Development and Innovation Laboratory, Butantan Institute, São Paulo 05359-900, Brazil.; Graduate Program in Medical Sciences, College of Medicine, University of São Paulo, São Paulo 05508-220, Brazil. |
| Abstrakt: |
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. |
