Anti-proliferative and cytotoxic activity of pentadactylin isolated from Leptodactylus labyrinthicus on melanoma cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Lithium thiazolidine-4-carboxylate: Synthesis, spectroscopic characterization and preliminary in vitro cytotoxic studies in human HeLa cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 μL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Myotoxic phospholipases A2 isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells

This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A2 (PLA2s) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing Mr ∼ 14,000 for the monomer and 28,000 Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA2s from snake venoms, MTX-I belonging to Asp49 PLA2 class, enzymatically active, and MTX-II to Lys49 PLA2s, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA2 and anticoagulant activities, corroborating the importance of residue His48 and Ca2+ ions for the enzymatic catalysis. Both PLA2s induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA2 proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer. © 2008 Elsevier Inc. All rights reserved.

Cytotoxic effects of white-MTA and MTA-Bio cements on odontoblast-like cells (MDPC-23)

This study evaluated the cytotoxic effects of 2 mineral trioxide aggregate (MTA) cements - White-MTA-Angelus and a new formulation, MTA-Bio - on odontoblast-like cell (MDPC-23) cultures. Twenty-four disc-shaped (2 mm diameter x 2 mm thick) specimens were fabricated from each material and immersed individually in wells containing 1 mL of DMEM culture medium for either 24 h or 7 days to obtain extracts, giving rise to 4 groups of 12 specimens each: G1 - White-MTA/24 h; G2 - White-MTA/7 days; G3 - MTA-Bio/24 h; and G4 - MTA-Bio/7 days. Plain culture medium (DMEM) was used as a negative control (G5). Cells at 30,000 cells/cm 2 concentration were seeded in the wells of 24-well plates and incubated in a humidified incubator with 5% CO 2 and 95% air at 37°C for 72 h. After this period, the culture medium of each well was replaced by 1 mL of extract (or plain DMEM in the control group) and the cells were incubated for additional 2 h. Cell metabolism was evaluated by the MTT assay and the data were analyzed statistically by ANOVA and Tukey's test (α=0.05). Cell morphology and the surface of representative MTA specimens of each group were examined by scanning electron microscopy. There was no statistically significant difference (p>0.05) between G1 and G2 or between G3 and G4. No significant difference (p>0.05) was found between the experimental and control groups either. Similar cell organization and morphology were observed in all groups, regardless of the storage periods. However, the number of cells observed in the experimental groups decreased compared to the control group. MTA-Bio presented irregular surface with more porosities than White-MTA. In conclusion, White-MTA and MTA-Bio presented low cytotoxic effects on odontoblast-like cell (MDPC-23) cultures.

Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production

Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or antioxidative stress), could be a cause of in vitro toxicity induced by these drugs. © 2013 Fares Zeidán-Chuliá et al.

Cytotoxic action of Brazilian propolis in vitro on canine osteosarcoma cells

Osteosarcoma (OSA) is a primary bone neoplasm frequently diagnosed in dogs. The biology of OSA in pet dogs is identical to that of pediatric patients, and it has been considered an excellent model in vivo to study human OSA. Since the individual response to chemotherapy is unpredictable and considering that propolis is a natural product with several biological properties, this work evaluated the cytotoxic action of propolis on canine OSA cells. The primary cell culture of canine OSA was obtained from the tumor of a dog with OSA. Cell viability was assessed after incubation with propolis, 70% ethanol (propolis solvent), and carboplatin after 6, 24, 48, and 72 h. Cell viability was analyzed by the crystal violet method. Data showed that canine OSA cells were sensitive to propolis in a dose- and time-dependent manner and had a distinct morphology compared to control. Its solvent (70% ethanol) had no effect on cell viability, suggesting that the cytotoxic action was exclusively due to propolis. Our propolis sample exerted a cytotoxic effect on canine OSA cells, and its introduction as a possible therapeutic agent in vivo could be investigated, providing a new contribution to OSA treatment. Copyright © 2012 John Wiley & Sons, Ltd.

Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Disperse Red 1 (textile dye) induces cytotoxic and genotoxic effects in mouse germ cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cytotoxic and genotoxic effects of ethanolic extract of Euphorbia hyssoptfolia L. on HepG2 cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MIT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3 h of exposure and with concentrations of 675 and 1520 ng/ml after 24 h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24 h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24 h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. (C) 2014 Elsevier GmbH. All rights reserved.

Antimicrobial and Cytotoxic Activity of Fruit Extract from Syzygium cumini (L.) Skeels

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Immunostimulatory and cytotoxic activities of Indigofera suffruticosa (Fabaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)