Antiproliferative and Genotoxic Action of an Underexploited Organoteluran Derivative on Sarcoma 180 Cells

Author(s):  
Maria L.L. Barreto do Nascimento ◽  
Antonielly Campinho dos Reis ◽  
José V.O. Santos ◽  
Helber A. Negreiros ◽  
Felipe C. Carneiro da Silva ◽  
...  

Background: The search for novel metallic chemical compounds with toxicogenic effects have been of great importance for more efficient cancer treatment. Objective: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in S-180 cell line. Methods: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesis-block micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5 µM. Results: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20 µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5 µM, which is thought to avoid an aggressive immune response of the organism. Conclusion: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.


Author(s):  
H. Norppa ◽  
M. Hayashi ◽  
T. Sofuni ◽  
Y. Kodama ◽  
M. Ishidate


2006 ◽  
Vol 25 (6) ◽  
pp. 477-485 ◽  
Author(s):  
James C. Griffiths ◽  
Ray A. Matulka ◽  
Ronan Power

Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast ( Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker’s yeast ( S. cerevisiae; Sel-Plex®), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex® showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex® did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex® did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex® is nongenotoxic.



2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Juliana Marques Senedese ◽  
Aline Rafaela Rodrigues ◽  
Michelle Andrade Furtado ◽  
Viviane Dias Faustino ◽  
Andresa A. Berretta ◽  
...  

Propolis possesses various biological activities such as antibacterial, antifungal, anti-inflammatory, anesthetic and antioxidant properties. A topically applied product based on Brazilian green propolis was developed for the treatment of burns. For such substance to be used more safely in future clinical applications, the present study evaluated the mutagenic potential of topical formulations supplemented with green propolis extract (1.2, 2.4 and 3.6%) based on the analysis of chromosomal aberrations and of micronuclei. In thein vitrostudies, 3-h pulse (G1phase of the cell cycle) and continuous (20 h) treatments were performed. In thein vivoassessment, the animals were injured on the back and then submitted to acute (24 h), subacute (7 days) and subchronic (30 days) treatments consisting of daily dermal applications of gels containing different concentrations of propolis. Similar frequencies of chromosomal aberrations were observed for cultures submitted to 3-h pulse and continuous treatment with gels containing different propolis concentrations and cultures not submitted to any treatment. However, in the continuous treatment cultures treated with the 3.6% propolis gel presented significantly lower mitotic indices than the negative control. No statistically significant differences in the frequencies of micronuclei were observed between animals treated with gels containing different concentrations of propolis and the negative control for the three treatment times. Under the present conditions, topical formulations containing different concentrations of green propolis used for the treatment of burns showed no mutagenic effect in either test system, but 3.6% propolis gel was found to be cytotoxic in thein vitrotest.



2018 ◽  
Vol 12 (1) ◽  
pp. 27-32 ◽  
Author(s):  
R. A. Islamov ◽  
I. Bishimova ◽  
A. N. Sabitov ◽  
A. I. Ilin ◽  
M. M. Burkitbaev


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dan Liu ◽  
Zhiding Wang ◽  
Huijuan Wang ◽  
Feifei Ren ◽  
Yanqin Li ◽  
...  

Abstract Lymphocyte apoptosis appears to play an important role in immunodysfunction in sepsis. We investigated the role of miR-223 in cell proliferation and apoptosis to identify potential target downstream proteins in sepsis. We recruited 143 patients with sepsis and 44 healthy controls from the Chinese PLA General Hospital. Flow cytometry was used to sort monocytes, lymphocytes, and neutrophils from fresh peripheral blood. A miR-223 mimic and inhibitor were used for transient transfection of Jurkat T cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to assess expression of the miRNAs in cells. Western blot analysis was performed to measure protein expression. We evaluated the cell cycle and apoptosis by using flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Expression of miR-223 was significantly higher in the survivor group than in the nonsurvivor group. Multiple linear regression analysis revealed that SOFA scores correlated negatively with miR-223 and monocyte counts, with β coefficients (95% CI) of − 0.048 (− 0.077, − 0.019) and − 47.707 (− 83.871, − 11.543), respectively. miR-223 expression also correlated negatively with the percentage of apoptosis in lymphocytes. The rate of apoptosis in the miR-223 mimic group was significantly lower than that of the negative control, with an adverse outcome observed in the miR-223 inhibitor group. We also found that miR-223 enhanced the proliferation of Jurkat T cells and that inhibiting miR-223 had an inhibitory effect on the G1/S transition. We conclude that miR-223 can serve as a protective factor in sepsis by reducing apoptosis and enhancing cell proliferation in lymphocytes by interacting with FOXO1. Potential downstream molecules are HSP60, HSP70, and HTRA.



Materials ◽  
2019 ◽  
Vol 12 (8) ◽  
pp. 1330 ◽  
Author(s):  
Conceição de Maria Vaz Elias ◽  
Antônio Luiz Martins Maia Filho ◽  
Laryssa Roque da Silva ◽  
Fabrício Pires de Moura do Amaral ◽  
Thomas J. Webster ◽  
...  

Here, butylene adipate-co-terephthalate/polypyrrole with nanohydroxyapatite (PBAT/PPy/nHAp) scaffolds were fabricated and characterized. The electrospinning process was carried out using 12 kV, a needle of 23 G, an infusion pump set at 0.3 mL/h, and 10 cm of distance. Afterwards, nHAp was directly electrodeposited onto PBAT/PPy scaffolds using a classical three-electrode apparatus. For in vivo assays (comet assay, acute and chronic micronucleus), 60 male albino Wistar rats with 4 groups were used in each test (n = 5): PBAT/PPy; PBAT/PPy/nHAp; positive control (cyclophosphamide); and the negative control (distilled water). Peripheral blood samples were collected from the animals to perform the comet test after 4 h (for damage) and 24 h (for repair). In the comet test, it was shown that the scaffolds did not induce damage to the % DNA tail and neither for tail length. After the end of 48 h (for acute micronucleus) and 72 h (for chronic micronucleus), bone marrow was collected from each rat to perform the micronucleus test. All of the produced scaffolds did not present genotoxic effects, providing strong evidence for the biological application of PBAT/PPy/nHAp scaffolds.





2011 ◽  
Vol 20 (No. 5) ◽  
pp. 181-191 ◽  
Author(s):  
P. Šmerák ◽  
H. Šestáková ◽  
Z. Polívková ◽  
I. Bárta ◽  
B. Turek ◽  
...  

Using the Ames bacterial mutagenicity test and an in vivo micronucleus test, we investigated the antigenotoxic effect of ellagic acid on the genotoxicity of three mutagens: amino-methylimidazo-quinoline (IQ), aflatoxin B1 (AFB1), and N-nitroso-N-methylurea (MNU). Ellagic acid is a naturally occurring phenolic compound which is found in a variety of soft fruits and vegetables. The effect of this compound on the immunosuppressive activity of mutagens was followed in vivo by the chemiluminescence test. In the Ames assay, ellagic acid at concentrations of 300 and 30 μg/plate demonstrably inhibits the mutagenic activity of two indirect mutagens: IQ and AFB1. The concentration of 300 μg/plate had the strongest effect on mutagenicity of all concentrations of IQ in strain TA98 of Salmonella typhimurium, whereas in strain TA100 concentration of 30 μg per dish of ellagic acid was more effective than 300 μg per plate. Also in combination with different concentrations of AFB1, ellagic acid proved to be a strong antimutagen. In this case the lower of the two effective concentrations – 30 μg/plate – had a much greater antimutagenic effect on both strains tested than 300 μg/plate. In combination with the direct mutagen MNU, ellagic acid did not show any marked antimutagenic effect at most of the concentrations tested in strain TA100. Only the highest concentrations of ellagic acid reduced the mutagenic effect of MNU weakly and only in combination with two lower concentrations of MNU. In the micronucleus test, three-day oral application of ellagic acid prior to the applicaton of AFB1, IQ, or MNU, respectively, markedly reduced the numbers of micronuclei induced by these three mutagens in polychromatophilic erythrocytes of mice. Chemiluminescence test with mouse granulocytes proved that ellagic acid not only prevents the inhibitory effects of mutagens on free oxygen radicals and hydrogen peroxide production, but that this production is stimulated by ellagic acid in combination with mutagens even to a greater extent than by ellagic acid alone. From these results we can deduce that ellagic acid repairs strong immunosuppressive effects of all mutagens applied.  



2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.



2011 ◽  
Vol 23 (No. 5) ◽  
pp. 202-208 ◽  
Author(s):  
M. Langová ◽  
Z. Polívková ◽  
P. Šmerák ◽  
J. Bártová ◽  
I. Bárta

Evidence exists from population-based and laboratory studies that some phytochemicals have protective effects against tumors or other diseases and reveal antimutagenic activity. We studied the protective effect of the plant phytoallexin resveratrol on the mutagenic activity of three mutagens, i.e. aflatoxin B<sub>1</sub> (AFB<sub>1</sub>), 2-amino-3-methylimidazo[4,5-f]qui-noline (IQ) and N-nitroso-N-methylurea (MNU) using the Ames and the micronucleus tests. In the Ames test, we proved a significant antimutagenic activity only against the indirect mutagens AFB<sub>1</sub> and IQ, not against the direct mutagen MNU. A significant decrease of mutagenicity of all three mutagens was detected by the micronucleus test. &nbsp;



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