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Response Proliferative Capacity of Undifferentiated Stem Cells of Obtained Human Adult Dental Follicle

Stem Cell Discovery 2014年第4期4卷 125-137页

作者： Larissa Kim Higashi de Carvalho Aline Vieira Pinheiro de Araujo manuela garcia laveli da silva Rosa Andréa Nogueira Laiso Durvanei Augusto Maria Faculty of Medicine University of Sao Paulo Sao Paulo Brazil Laboratory of Biochemistry and Biophysics Butantan Institute Sao Paulo Brazil

Objective: The aim of this study was correlation proliferative activity, markers express stem cells, and lipid peroxides of undifferentiated stem cells of human adult dental follicle (DF) following culture. Methods: For this study, we used 8 samples from DF of impacted third molars to maintain culture conditions and evaluated the growth curve, cell viability, production of lipid peroxidation, cell cycle phases, and proliferative index during 25 days of culture. Results: Cells after culture showed characteristics of fibroblast-like type following 25th day of culture. The results of lipid peroxidation showed that stem cells in culture produce 13 nmoles/ml malondialdehyde at the start of culture, increasing until the 12th day and then began a decline that lasted until the 25th day. We revealed that DFSCs presented a significantly higher percentage of cells in S + G2/M phases by the 15th day of culture compared with cells at the start of culture. Cell surface markers revealed that cell lines were negative for HLA-DR and positive for CD90, CD44, and CD105. The expression of p21 protein, involved in the regulation of the cell cycle, showed a significant increase from the 15th to 25th day of culture. Results of cell division rates show a significant increase between the 6th and 15th day of culture. Conclusions: We conclude that the culture remained stable during the 25 days of culture, presenting the markers of stem cells and markers of control, progression, and cell proliferation that there was an increased production of lipid peroxides between the 6th and 12th days;this increase is related to the increased numbers of cells that also occurs during this period. Then, there is a significantly decline in the production of lipid peroxides and the number of cells, which is accompanied by an increase in cell unviability.

关键词： Follicle Dental Stem Cells Lipid Peroxidation Cell Cycle Proliferation

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Meclizine Chloridrate and Methyl-β-Cyclodextrin Associated with Monophosphoester Synthetic Phosphoethanolamine Modulating Proliferative Potential in Triple-Negative Breast Cancer Cells

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Journal of Pharmacy and Pharmacology 2019年第7期7卷 408-420页

作者： manuela garcia laveli da silva Luciana Bastianelli Knop Durvanei Augusto Maria Molecular Biology Laboratory Butantan InstituteSao PauloSPBrazil

Synthetic phosphoethanolamine(Pho-s)is a monophosphoester ester with anti-inflammatory and pro-apoptotic *** chloridrate(MC)is a histamine H1 receptor blocker that is also able to inhibit cellular ***,MC does not inhibit cellular respiration in isolated mitochondria such as antimycin and ***-β-cyclodextrin(MβCD)belongs to theβ-cyclodextrin family,which is capable of removing cholesterol from the plasma *** aim of this study was to evaluate the proliferative effects of meclizine chloridrate and methyl-β-cyclodextrin compounds associated with synthetic phosphoethanolamine in a triple-negative human breast tumor line,Mda-MB-231 Cell viability of the tumor line and normal cells FN1 was evaluated by MTT colorimetric test;the production of free radicals was determined by lipoperoxidation(LPO)test;and the percentage of cell cycle phases and proliferative index was evaluated by flow *** viability demonstrated a significant decrease with the treatments of MβCD,MC and Pho-s associated with *** production of free radicals decreases significantly in all *** addition,a significant increase of DNA fragment and decrease in G0/G1 cell cycle phase were observed in cellular percentage with concentrations of 20 and 30 mM of Pho-s in association with MC and MβCD,respectively.

关键词： Human triple-negative breast cancer Mda-MB-231 synthetic phosphoethanolamine meclizine chloridrate methyl-β-cyclodextrin cell cycle

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Phosphomonoester Phosphoethanolamine Induces Apoptosis in Human Chronic Myeloid Leukemia Cells

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Journal of Pharmacy and Pharmacology 2019年第7期7卷 434-450页

作者： Thais de Oliveira Conceicao manuela garcia laveli da silva Durvanei Augusto Maria Molecular Biology Laboratory Butantan InstituteSao PauloSPBrazil

Background:Leukemia is a type of cancer that starts in the blood or blood-forming *** results from the clonal proliferation of hematopoietic cells in the bone marrow and/or lymphoid tissues,which subsequently reach the peripheral circulation and can infiltrate other *** are many different kinds of leukemia,and treatments are different for each *** leukemia is with a slower growing than acute leukemia but could be just as *** are antitumor analogs,such as synthetic phosphoethanolamine,which is a phosphorylated compound capable of controlling cellular proliferation and inducing apoptosis in several types of tumor ***:K562 and K562-Lucena(MDR+)human chronic myeloid leukemia cells were treated with synthetic phosphoethanolamine(Pho-s).The viability was evaluated by sulforhodamine B(SRB)assay and cell cycle phases,apoptosis,markers expression,and mitochondrial potential were assessed by flow ***:Tumor cells formed clusters in suspension and decreased significantly *** concentrations for IC50%were ***-s treated were 43.1 mM(K562)and 145.9 mM(K562-Lucena MDR+)in a period of 24 ***-s induced changes in the distribution of cell population phases of cell cycle which showed an increase in fragmented DNA and increased markers expression envolved apoptosis pathways a decrease in the G1/G0 ***:Treatment of K562 and K562-Lucena(MDR+)chronic myeloid leukemia cells with Pho-s showed dose and time dependent cytotoxic *** cytotoxicity induced a decrease in proliferative capacity,mitochondrial electrical potential,and consequently release of cytochrome C;inhibition of Bcl-2 family protein expression,increase in pro-apoptotic family members Bad and Bax,dependent on p53 ***:This study presented a significant therapeutic potential of Phos-s in this type of leukemia through the apoptotic effects on tumor cells independently of the molecular resistance

关键词： Chronic myeloid leukemia cells synthetic phosphoethanolamine mitochondrial potential apoptosis cell cycle

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2-aminoethyl Dihydrogen Phosphate as a Modulator of Proliferative and Apoptotic Effects in Breast Cancer Cell Lines

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Journal of Pharmacy and Pharmacology 2021年第3期9卷 83-97页

作者： manuela garcia laveli da silva Laertty garcia de Sousa Cabral Monique Gonçalves Alves Thais deOliveira Conceição Henrique Hesse Rosa Andrea Nogueira Laiso daniel da Conceição Rabelo Durvanei Augusto Maria Development and Innovation Laboratory Butantan InstituteSao PauloSP 05503-900Brazil Faculty of Medicine University of São PauloSao PauloSP 01246-000Brazil

Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from existing molecules fortheir absorption, stability and display anti-inflammatory, anti-proliferative and pro-apoptotic properties. Methods: MCF-7 humanbreast adenocarcinoma cells were treated with 2-AEH2P. The viability and adhesion cells were evaluated by MTT assay. Cell cyclephases, apoptosis, markers and mitochondrial potential were assessed by flow cytometry. Morphological ultrastructural analyzeswere performed by laser confocal microscopy. Results: MCF-7 Tumor cells acquired round shapes, lost cytoplasmic expansions,formed clusters in suspension and decreased significantly viability. There were changes in the morphology, membrane fragmentationand loss of cytoplasmic projection. The obtained concentrations for IC50% were 37.2;25.8;1.8 mM for periods of 24, 48 and 72 h,respectively. Changes in the distribution of cell population phases of the cell cycle showed an increase in fragmented DNA and anincrease in the G2/M phase. The expression β-gal showed proliferative reduction induced by 2-AEH2P. Laser confocal microscopyshowed changes in the mitochondrial membrane and alteration in distribution. Proliferative index of MCF-7 tumor cells treated with2-AEH2P decreased significantly when compared to fibroblast normal cells. The compound 2-AEH2P is a phospholipid withantiproliferative potential and apoptosis modulator.

关键词： Human Breast Adenocarcinoma MCF-7 2-AEH2P Antitumor Apoptosis Cell cycle Senescence

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