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
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
Glioblastoma multiforme (GBM) is the most common type of malignant primary astrocytoma. It accounts for over 60% of all brain tumors in adults. Despite the variety of modern therapies against GBM, it is still a deadly disease with extremely poor prognosis. Patients usually have an average survival of approximately 14 to 15 months from diagnosis. The aim of this study was to evaluate the cytotoxic and antiproliferative effects of three monophosphoesters (MFE) on U-138 human glioblastoma multiforme cells. The determination of cytotoxic activity of the compounds was evaluated by the MTT colorimetric method. Treatment with MFE-1 presented cytotoxicity to tumor cell U-138, with IC50 values 18.16 and 11.6 mM in the 24 and 48h period, generating morphological changes of toxicity. For the treatment with MFE-2 the IC50% value was 30.22 and 25mM in the 24 and 48h periods, with significant changes in morphology and reduction of confluence. Compound MFE-3 was not effective for in vitro treatment of U-138 tumor cells, with IC50% values 76.74 and 67.8 mM. When comparing the compounds with respect to their in vitro effectiveness, their antiproliferative and cytotoxic capacity for the U-138 glioblastoma multiforme cell, monophosphoester 1 had a lower IC50% in both treatment periods, 24 and 48h, compared to the other compounds. Monophosphoester 3 did not present a significant result, obtaining an IC50% 4 times higher than monophosphoester 1 in the 24h and approximately 6 times higher when comparing the value obtained for the 48h treatment.
O glioblastoma multiforme (GBM) é o tipo de astrocitoma primário maligno e de maior ocorrência. É responsável por mais de 60% de todos os tumores cerebrais em adultos. Apesar da variedade de terapias modernas contra o GBM, ainda é uma doença mortal com prognóstico extremamente ruim. Os pacientes geralmente têm uma sobrevida média de aproximadamente 14 a 15 meses a partir do diagnóstico. O objetivo deste estudo foi avaliar os efeitos citotóxicos e antiproliferativos de três monofosfoesteres (MFE) em células de glioblastoma multiforme humano U-138. A determinação da atividade citotóxica dos compostos foi avaliada pelo método colorimétrico MTT. O tratamento com o MFE-1 apresentou citotoxicidade para a célula tumoral U-138, com valores de IC50% 18,16 e 11,6 mM no período de 24 e 48h, gerando alterações morfológicas de toxicidade. Para o tratamento com MFE-2 o valor de IC50% foi de 30,22 e 25mM nos períodos de 24 e 48h, com alterações significativas na morfologia e redução da confluência. O composto MFE-3 não foi efetivo para o tratamento in vitro das células tumorais U-138, com valores de IC50% 76,74 e 67,8 mM. Quando comparando os compostos em relação à efetividade in vitro, sua capacidade antiproliferativa e citotóxica para a célula de glioblastoma multiforme U-138, Ciências da Saúde: Campo Promissor em Pesquisa Capítulo 23 216 o monofosfoester 1 apresentou menor IC50% em ambos os períodos de tratamento, 24 e 48h, em comparação com os demais compostos testados. O MFE-3 não apresentou um resultado significativo, obtendo um IC50% 4 vezes maior que o monofosfoester 1 no período de 24h e aproximadamente 6 vezes maior quando comparando o valor obtido para o período de 48h.