ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Triple-negative breast cancer is the most aggressive subtype of breast cancer, with worse clinical evolution and tumor-free survival, leading to the need to develop new effective therapies for its control. The present study evaluated the action of tumor-penetrating peptide BR2 associated with 2-aminoethyl dihydrogen phosphate (2-AEH2P) on triple-negative breast tumor cells. Cell viability was evaluated by the MTT colorimetric method, mitochondrial electrical potential, and proteins involved in cell proliferation and death control were evaluated by flow cytometry and structural and morphological analysis by confocal microscopy. The results obtained showed that the peptide BR2 and the association 2-AEH2P + BR2 promoted significant cytotoxicity in tumor lines, compared to 2-AEH2P alone. In addition, the association 2-AEH2P + BR2 promoted tumor cells arrest in the G0/G1 phases. Interestingly, both treatments modulated the expression of markers CD44, CD34, CD24, cyclin D1, and Bcl-2, increased p21, Bax, and released cytochrome c. The association proved to be more effective, providing modulation of proteins involved in cell death and senescence, more pronounced cytotoxicity for tumor cells compared to normal cells, and the reduction of markers related to aggressiveness profile, progression, and tumor metastasis.
ABSTRACT
The main obstacle in the treatment of cancer patients has been resistance to multiple drugs, leading to the need to develop molecules with a higher specificity target. The liposomal formulation DODAC/2-AEH2P has antitumor potential, inducing apoptosis in several tumor types. Human chronic myeloid leukemia K-562 and K-562 Lucena (MDR+) cells were treated with the DODAC carrier and the liposomal formulation 2-AEH2P. Viability, cell cycle phases, apoptosis, marker expression and mitochondrial potential were analyzed. Significant reduction in viability was observed for all treatments. Changes in the distribution of the cell cycle phases and expression of markers involved in the apoptosis pathways were observed. Reduction of the mitochondrial electrical potential mediated by Bcl-2, being regulated by the reduction of the MTCH2 protein linked to the progression of myeloid leukemia and an increase in the pro-apoptotic proteins Bad and Bax, dependent on p53. This study demonstrated a significant therapeutic potential through apoptotic effects in leukemic cells, regardless of the molecular resistance profile (MDR+).
ABSTRACT
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.
Subject(s)
Melanoma, Experimental/surgery , Mesenchymal Stem Cell Transplantation , Angiogenic Proteins/metabolism , Animals , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Cell Cycle Checkpoints , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation , Female , Melanoma, Experimental/immunology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice, Inbred C57BL , Tumor BurdenABSTRACT
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.
ABSTRACT
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.
