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Cytotoxic Potential (cytotoxic + potential)
Selected AbstractsIn vitro evaluation of the clastogenicity of fumagillinENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2008Jevrosima Stevanovic Abstract Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is effective against microsporidia and various Amoeba species, but is also toxic when administered systemically to mammals. Furthermore, a recent in vivo study by Stanimirovic Z et al. 2007: (Mutat Res 628:1,10) indicated genotoxic effects of fumagillin. The aim of the present study was to investigate and explain the clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine salt) on human peripheral blood lymphocytes in vitro by sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The mitotic index (MI), proliferation index (PI), and nuclear division index (NDI) were calculated to evaluate the cytotoxic potential of fumagillin. Five concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 ,g/ml) were applied to lymphocyte cultures. All the tested concentrations of fumagillin increased the frequency of SCE per cell significantly (P < 0.001 or P < 0.01) compared with the negative control. A significant (P < 0.001) increase in frequency of structural CA was observed at the three highest concentrations in comparison with the negative control. In addition, the three highest test concentrations increased MN formation and decreased MI, PI, and NDI significantly compared with the negative control. The present results indicate that fumagillin is clastogenic and cytotoxic to cultured human lymphocytes. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] Killers and beyond: NK-cell-mediated control of immune responsesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Christopher E. Andoniou Abstract Effective immunity requires coordinated activation of innate and adaptive immune responses. NK cells are principal mediators of innate immunity, able to respond to challenge quickly and generally without prior activation. The most acknowledged functions of NK cells are their cytotoxic potential and their ability to release large amounts of cytokines, especially IFN-,. Recently, it has become clear that NK cells are more than assassins. Indeed, NK cells play critical roles in shaping adaptive immunity. [source] Evaluation of cytogenetic effects of lambda-cyhalothrin on human lymphocytesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2005Rambabu Naravaneni Abstract The genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated on human lymphocytes cultured in vitro. Utilizing the trypan blue dye exclusion technique assay, the LC50 of LCT was found to be 28 , M. Based on the LC50 value, it is seen that LCT was highly toxic to lymphocyte cultures, among other pyrethroid group of pesticides. Chromosomal aberrations induced by LCT were determined using metaphase plate-spreads of lymphocytes. The chromosomal analysis was recorded using Medi-Image software technology. The analysis revealed that more satellite associations and gaps were found, which were statistically significant (p < 0.05) when compared to controls. Comet assay was used to assess the possibility of LCT to induce the damage in DNA, where the increase in comet tail length relates to the extent of DNA single strand breaks. The results presented here indicate that in vitro assays could be used as indicators of cytotoxicity and genotoxicity of the pesticide. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:304,310, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20095 [source] Antiplasmodial and cytotoxic activity of khellactone derivatives from Angelica purpuraefolia chungPHYTOTHERAPY RESEARCH, Issue 3 2010Ill-Min Chung Abstract The methanolic extract of the rhizomes parts of Agelica purpuraefolia was investigated for its activity against chloroquine-sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two natural khellactone, (+)-4,-Decanoyl- cis -khellactone (1) and (+)-3,-Decanoyl- cis -khellactone (2) were isolated from the rhizomes parts of A. purpuraefolia. Two compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK-OV-3 cancer cell line cells. Compounds 1, 2 showed notable growth inhibitory activity against chloroquine-sensitive strains of Plasmodium falciparum with IC50 values from 1.5 and 2.4,,M. This compound showed no significant cytotoxicity (IC50 > 100,,M) evaluated using SK-OV-3 cancer cell line cells. This is the first report on the antiplasmodial activity of the compounds from A. purpuraefolia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Inhibition of term decidual NK cell cytotoxicity by soluble HLA-G1AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5-6 2006Tobias G. Poehlmann Objectives, Soluble (s)HLA-G1 is produced by trophoblast cells. Aim was to analyze the capacities and mechanisms of sHLA-G1 to regulate interleukin (IL)-2-induced cytotoxicity of natural killer (NK) cells from human deciduas. Methods, Natural killer cells were isolated from decidual layers of term placentae, stimulated or not with IL-2 and supplemented with various concentrations of recombinant soluble HLA-G1 (sHLA-G1). For NK cell cytotoxicity assays, K562 cells were used as targets. Expression of signal transducer and activator of transcription 3 (STAT3) and perforin was analyzed by Western blotting. Apoptosis was examined by assessment of poly(ADP-ribose) polymerase cleavage. NK cells were analyzed by flow cytometry for IL-2receptor- , (IL-2R,; CD25) and transferrin receptor CD71 expression. Results, Interleukin-2 increases CD71, STAT3, perforin expression and cytotoxic potential of NK cells. Expression of CD71, STAT3 and perforin decreased simultaneously with cytotoxicity and dose-dependently when sHLA-G1 (1.6 ,g/mL,1.6 ng/mL) was added to IL-2 stimulated cultures. sHLA-G1 did not induce apoptosis and CD25 expression was not affected. Conclusion, Interleukin-2R, expression is not controlled by sHLA-G1, but its signal transducer STAT3 as well as several downstream effects, such as perforin expression, proliferation and cytotoxicity. The control of STAT3 bioavailability through sHLA-G1 may be a key regulator of the mentioned effects. [source] Synthesis and Biological Evaluation of Some Novel Polysubstituted Pyrimidine Derivatives as Potential Antimicrobial and Anticancer AgentsARCHIV DER PHARMAZIE, Issue 5 2009Sherif A. F. Rostom Abstract Synthesis and evaluation of the antimicrobial and cytotoxic activity of two series of polysubstituted pyrimidines comprising the thioether functionality and other pharmacophores, reported to contribute to various chemotherapeutic activities are described. All newly synthesized compounds were subjected to in-vitro antibacterial and antifungal screening. Out of the compounds tested, 18 derivatives displayed an obvious inhibitory effect on the growth of the tested Gram-positive and Gram-negative bacterial strains, with special effectiveness against the Gram-positive strains. Compounds 1, 2, 6, 7, 9, 10, 11, 21, and 24 revealed remarkable broad antibacterial spectrum profiles. Among those, compounds 1, 2, 6, 7, 9, and 24 exhibited an appreciable antifungal activity against C. albicans. Compound 2 proved to be the most active antimicrobial member identified here as it showed twice the activity of ampicillin against B. subtilis and the same activity of ampicillin against M. Luteus and P. aeruginosa together with a moderate antifungal activity. Further, eleven analogs were evaluated for their in-vitro cytotoxic potential utilizing the standard MTT assay against a panel of three human cell lines: breast adenocarcinoma MCF7, hepatocellular carcinoma HePG2, and colon carcinoma HT29. The obtained data revealed that six of the tested compounds 1, 3, 7, 12, 13, and 15 showed a variable degree of cytotoxic activity against the tested cell lines at both the LC50 and LC90 levels. Compound 7 proved to be the most active cytotoxic member in this study with special effectiveness against the colon carcinoma HT29 and breast cancer MCF7 human cell lines for LC50 and LC90. Thus, compounds 1 and 7 could be considered as possible dual antimicrobial-anticancer agents. [source] | |||||||||||||