scholarly journals Antiproliferative activity of new benzimidazole derivatives.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Katarzyna Błaszczak-Świątkiewicz ◽  
Paulina Olszewska ◽  
Elżbieta Mikiciuk-Olasik

A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells.

2009 ◽  
Vol 37 (2) ◽  
pp. 209-218 ◽  
Author(s):  
Mathieu Vinken ◽  
Elke Decrock ◽  
Elke De Vuyst ◽  
Luc Leybaert ◽  
Tamara Vanhaecke ◽  
...  

This study was set up to critically evaluate a commonly-used in vitro model of hepatocellular apoptotic cell death, in which freshly isolated hepatocytes, cultured in a monolayer configuration, are exposed to a combination of Fas ligand and cycloheximide for six hours. A set of well-acknowledged cell death markers was addressed: a) cell morphology was studied by light microscopy; b) apoptotic and necrotic cell populations were quantified by in situ staining with Annexin-V, Hoechst 33342 and propidium iodide (PI); c) apoptotic and necrotic activities were monitored by probing caspase 3-like activity and measuring the extracellular leakage of lactate dehydrogenase (LDH), respectively; and d) the expression of apoptosis regulators was investigated by immunoblotting. The initiation of apoptosis was evidenced by the activation of caspase 8 and caspase 9, and increased Annexin-V reactivity. Progression through the apoptotic process was confirmed by the activation of caspase 3 and Bid, the enhanced expression of Bax, and the occurrence of nuclear fragmentation. Late transition to a necrotic appearance was demonstrated by an increased number of PI-positive cells and augmented extracellular release of LDH. Thus, the in vitro model allows the study of the entire course of Fas-mediated hepatocellular apoptotic cell death, which is not possible in vivo. This experimental system can serve a broad range of in vitro pharmaco-toxicological purposes, thereby directly assisting in the reduction of animal experimentation.


2002 ◽  
Vol 30 (02n03) ◽  
pp. 307-314 ◽  
Author(s):  
Hui-Chiu Chang ◽  
Wen-Chun Hung ◽  
Ming-Shyan Huang ◽  
Hseng-Kuang Hsu

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Alex Zagariya ◽  
Monica Sierzputovska ◽  
Shan Navale ◽  
Dharmapuri Vidyasagar

Background. We previously showed that meconium cuases lung cell death by apoptosis and inflammatory cytokine expression. Whether this is due to meconium exposure itself, or meconium related hypoxia remains unclear.Objectives. To elucidate the effects of meconium, saline, milk, hypoxia and hyperoxia induced lung injury.Design/Methods. We studied 5 groups of rabbit pups: (I) normal saline; (II) Milk; (III) 10% solution of meconium; (IV) only to 15 minutes of hypoxia (10% O2), and (V) 5 minutes of hypoxia (95% O2). After exposure lung lavage cells were used for apoptotic cell count and cytokine expression.In vitroresponse of human A 549 epithelial cells to meconium-and milk exposure was also studied.Results. There was no difference in cell death between saline and milk groups. However, meconium caused a significant cell loss compared to saline and milk—Inflammatory cytokines increased significantly in meconium group compared to saline or milk group. Although hypoxic and hyperoxic lungs showed increased inflammatory reaction compared to saline-treated lungs, this injury was not significant compared to meconium group. Studies with A549 cells also showed similar results.Conclusions. We conclude that lung cell injury in meconium aspiration is maily from meconium itself.


Metallomics ◽  
2015 ◽  
Vol 7 (5) ◽  
pp. 816-827 ◽  
Author(s):  
Yosuke Tabei ◽  
Akinari Sonoda ◽  
Yoshihiro Nakajima ◽  
Vasudevanpillai Biju ◽  
Yoji Makita ◽  
...  

Indium tin oxide (ITO) nanoparticles are taken up by human lung adenocarcinoma cells and the nanoparticles induce oxidative stress and DNA damage.


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