BackgroundMalignant melanoma is a less common but highly dangerous form of skin cancer; it starts in the melanocytes cells found in the outer layer of the skin. Jararhagin toxin, a metalloproteinase isolated from Bothrops jararaca snake venom acts upon several biological processes, as inflammation, pain, platelet aggregation, proliferation and apoptosis, though not yet approved for use, may one day be employed to treat tumors.MethodsB16F10 murine melanoma cells were treated with jararhagin (jara), a disintegrin-like metalloproteinase isolated from Bothrops jararaca snake venom, and jari (catalytic domain inactivated with 1,10-phenanthroline). Viability and adhesion cells were evaluated by MTT assay. The expression of caspase-3 active, phases of the cell cycle and apoptosis were assessed by flow cytometry. We analyze in vivo the effects of jararhagin on melanoma growth, apoptosis and metastasis.ResultsThe tumor cells acquired round shapes, lost cytoplasmic expansions, formed clusters in suspension and decreased viability. Jari was almost 20 times more potent toxin than jara based on IC50 values and on morphological changes of the cells, also observed by scanning electron microscopy. Flow cytometry analysis showed 48.3% decrease in the proliferation rate of cells and 47.2% increase in apoptosis (jara) and necrosis (jari), following 1.2 μM jara and 0.1 μM jari treatments. Caspase-3 activity was increased whereas G0/G1 cell cycle phase was on the decline. Proliferative rate was assessed by staining with 5,6-carboxyfluoresceindiacetate succinimidyl ester, showing a significant decrease in proliferation at all concentrations of both toxins.ConclusionsIn vivo treatment of the toxins was observed reduction in the incidence of nodules, and metastasis and antiproliferative inhibition capacity. This data strengthens the potential use jararhagin as an anti-neoplastic drug.

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Synthetic phosphoethanolamine (Pho-s) is a monophosphoester ester with anti-inflammatory and pro-apoptotic properties. Meclizine chloridrate (MC) is a histamine H1 receptor blocker that is also able to inhibit cellular respiration. However, MC does not inhibit cellular respiration in isolated mitochondria such as antimycin and rotenone. Methyl-β-cyclodextrin (MβCD) belongs to the β-cyclodextrin family, which is capable of removing cholesterol from the plasma membrane. The 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 cytometry. Cell viability demonstrated a significant decrease with the treatments of MβCD, MC and Pho-s associated with MC. The production of free radicals decreases significantly in all treatments. In 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.

Background: Leukemia is a type of cancer that starts in the blood or blood-forming tissues. It 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 systems. There are many different kinds of leukemia, and treatments are different for each one. Chronic leukemia is with a slower growing than acute leukemia but could be just as life-threatening. Phospholipids 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 cells. Methods: 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 cytometry. Results: Tumor cells formed clusters in suspension and decreased significantly viability. The concentrations for IC50% were obtained. Pho-s treated were 43.1 mM (K562) and 145.9 mM (K562-Lucena MDR+) in a period of 24 hours. Pho-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 phase. Discussion: Treatment of K562 and K562-Lucena (MDR+) chronic myeloid leukemia cells with Pho-s showed dose and time dependent cytotoxic effects. This 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 expression. Conclusion: 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 profile (MDR+).

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.