Cytotoxic Effect of Andrographis paniculata Associated with 2-Aminoethyl Dihydrogen Phosphate in Triple-Negative Breast Cells.

Cancer stands out as a major global public health concern and a significant impediment to increasing life expectancy worldwide. Natural bioactives derived from plants are renowned for their efficacy in treating various types of cancer. Andrographis paniculata (Burm.f.) is a well-known plant traditionally employed in diverse medical systems across the globe. The 2-AEH2P monophosphoester, a molecule intricately involved in phospholipid turnover, demonstrates antiproliferative effects across a broad spectrum of cancer types. This study aims to assess the antitumor, antiproliferative, and pharmacological effects of andrographolide at different concentrations, both individually and in conjunction with 2-aminoethyl dihydrogen phosphate. The cytotoxicity of the treatments was evaluated using the colorimetric MTT method, cell cycle phases, mitochondrial electrical potential, and markers expression via flow cytometry, while the pharmacological effects were assessed using SynergyFinder software 3.0. Treatments with A. paniculata, isolated at concentrations of 10%, 30%, and 50% of andrographolide, induced cell death in tumor cells, resulting in a reduction in mitochondrial electrical potential and alterations in cell cycle phases, particularly a decrease in the population of MDA MB-231 cells in the G0/G1 phase. The combination treatments exhibited significant cytotoxicity toward tumor cells, with minimal toxicity observed in normal fibroblast cells FN1. This led to a reduction in mitochondrial electrical potential and cell cycle arrest in the S phase for MDA MB-231 cells. Across all concentrations, the combined treatments demonstrated a synergistic pharmacological effect, underscoring the efficacy of the association. There was a change in the markers involved in cell death, such as p53, caspase 3, Bcl-2, and cytochrome c, suggesting the induction of regulated cell death. Markers associated with progression and proliferation, such as cyclin D1 and p21, corroborate the findings for cytotoxicity and cell cycle arrest.

Antiproliferative Modulation and Pro-Apoptotic Effect of BR2 Tumor-Penetrating Peptide Formulation 2-Aminoethyl Dihydrogen Phosphate in Triple-Negative Breast Cancer.

Breast cancer is the most common cancer in women, the so-called "Triple-Negative Breast Cancer" (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings.

Antitumor effect of cell therapy with mesenchymal stem cells on murine melanoma B16-F10.

In this study, the antitumor and immunomodulatory effects of mesenchymal stem cells (MSC) obtained from bone marrow in the treatment of dorsal melanoma B16-F10. The MSC cells were obtained from the bone marrow of isogenic C57BL/6J mice, characterized and inoculated by two routes, intratumor (it) and intravenous (iv). The hematological profile, expression markers and receptors, phases of the cell cycle and mitochondrial electrical potential were evaluated by flow cytometry. The dorsal tumor mass showed a significant reduction after treatment by the two routes of administration with a significant effect by the intravenous route. MSC showed immunomodulatory potential and did not induce an increase in the markers involved in tumor control and progression. The number of cells in the sub-G1 phase increased significantly after treatments compared to the control group. The percentage of cells in phases G0/G1, S and G2/M decreased, with only the group (it) showing a significant reduction. The intratumor group showed a significant decrease in the G2/M phase. Treatment with MSC provided a significant decrease in the percentage of metabolically active tumor cells, demonstrating its intrinsic effect in the control of cell proliferation. Regarding the mechanism of cell death, MSCs modulated the expression of proteins involved in the regulation of the cell cycle, angiogenesis receptors and pro-apoptotic proteins by intrinsic and extrinsic routes. Therefore, the use of undifferentiated MSC, administered intratumor and intravenous is possibly a promising treatment for melanoma.