Cytotoxic effects of cisplatin, cis-dichlorodiammineplatinum(II), on Tetrahymena

1988 ◽  
Vol 90 (4) ◽  
pp. 707-716
Author(s):  
J.R. Nilsson
Keyword(s):  
Mitochondrial Membrane ◽  
Prolonged Treatment ◽  
Dependent Manner ◽  
Inner Mitochondrial Membrane ◽  
Cell Organelles ◽  
Cell Content ◽  
Cytotoxic Effects ◽  
Dense Granules ◽  
High Concentrations ◽  
Dose Dependent

A study was made of the effects of cisplatin, cis-dichlorodiammineplatinum(II) (5–250 mg l-1), on the physiology and fine structure of Tetrahymena. The physiological effects observed were dose-dependent. Endocytosis was inhibited reversibly in all, but late in the high, concentrations. After an initial dose-related increase, due to division of cells most advanced in the cell cycle, proliferation ceased for at least two normal cell generations (6 h) in 50 and 100 mg drug l-1, but for 24 h in 250 mg l-1, after which multiplication was resumed in a dose-dependent manner. Exposure to cisplatin resulted in the appearance of small, refractive granules and platinum (i.e. electron-dense material) accumulated in these granules. Fine structural observations of cells exposed to 250 mg drug l-1 showed nucleolar fusion and appearance initially of lipid droplets, dense granules and autophagosomes. A time-dependent redistribution of cell organelles was revealed by morphometry; in particular, the mitochondria increased in number, but decreased in size. Moreover, after prolonged treatment (24 h) and without cell division, the inner mitochondrial membrane had diminished and the ratio of the inner to the outer mitochondrial membrane was only half of the value for control mitochondria. Concomitantly with this decrease, the cell content of ATP was reduced to a similar extent. The findings indicate a specific action of cisplatin on mitochondria, resembling that induced in Tetrahymena by chloramphenicol and methotrexate.

Synthesis and Biological Evaluation of Novel Heterocyclic Imines Linked Coumarin- Thiazole Hybrids as Anticancer Agents

2019 ◽  
Vol 19 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Nerella S. Goud ◽  
Mahammad S. Ghouse ◽  
Jatoth Vishnu ◽  
Jakkula Pranay ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Fluorescence Spectroscopy ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Dose Dependent

Background: Human Galectin-1, a protein of lectin family showing affinity towards β-galactosides has emerged as a critical regulator of tumor progression and metastasis, by modulating diverse biological events including homotypic cell aggregation, migration, apoptosis, angiogenesis and immune escape. Therefore, galectin-1 inhibitors might represent novel therapeutic agents for cancer. Methods: A new series of heterocyclic imines linked coumarin-thiazole hybrids (6a-6r) was synthesized and evaluated for its cytotoxic potential against a panel of six human cancer cell lines namely, lung (A549), prostate (DU-145), breast (MCF-7 & MDA-MB-231), colon (HCT-15 & HT-29) using MTT assay. Characteristic apoptotic assays like DAPI staining, cell cycle, annexin V and Mitochondrial membrane potential studies were performed for the most active compound. Furthermore, Gal-1 inhibition was confirmed by ELISA and fluorescence spectroscopy. Results: Among all, compound 6g 3-(2-(2-(pyridin-2-ylmethylene) hydrazineyl) thiazol-4-yl)-2H-chromen-2- one exhibited promising growth inhibition against HCT-15 colorectal cancer cells with an IC50 value of 1.28 ± 0.14 µM. The characteristic apoptotic morphological features like chromatin condensation, membrane blebbing and apoptotic body formation were clearly observed with compound 6g on HCT-15 cells using DAPI staining studies. Further, annexin V-FITC/PI assay confirmed effective early apoptosis induction by treatment with compound 6g. Loss of mitochondrial membrane potential and enhanced ROS generation were confirmed with JC-1 and DCFDA staining method, respectively by treatment with compound 6g, suggesting a possible mechanism for inducing apoptosis. Moreover, flow cytometric analysis revealed that compound 6g blocked G0/G1 phase of the cell cycle in a dose-dependent manner. Compound 6g effectively reduced the levels of Gal-1 protein in a dose-dependent manner. The binding constant (Ka) of 6g with Gal-1 was calculated from the intercept value which was observed as 1.9 x 107 M-1 by Fluorescence spectroscopy. Molecular docking studies showed strong interactions of compound 6g with Gal-1 protein. Conclusion: Our studies demonstrate the anticancer potential and Gal-1 inhibition of heterocyclic imines linked coumarin-thiazole hybrids.

scholarly journals Anthracycline-induced cytotoxicity in the GL261 glioma model system

2021 ◽  
Author(s):  
Amber M. Tavener ◽  
Megan C. Phelps ◽  
Richard L. Daniels
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Effects ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

Effect of galanin on glucose-, arginine-, or potassium-stimulated insulin release

1989 ◽  
Vol 256 (5) ◽  
pp. E619-E623
Author(s):  
T. Yoshimura ◽  
J. Ishizuka ◽  
G. H. Greeley ◽  
J. C. Thompson
Keyword(s):  
Insulin Release ◽  
High Glucose ◽  
Second Phase ◽  
Dependent Manner ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Second Phases ◽  
High Concentrations ◽  
Dose Dependent ◽  
Stimulation Of

We have examined the effect of galanin infusion on glucose-stimulated release of insulin from the isolated perfused pancreas of the rat to better characterize the effect of galanin on the first and second phases of insulin release. The effects of galanin on insulin release stimulated by L-arginine or high concentrations of potassium were also examined. When perfusion of galanin was started 4 min before the start of perfusion of high glucose (16.7 mM), galanin (10(-8)-10(-11) M) inhibited both the first and second phases of insulin release in a dose-dependent manner. When perfusion of galanin (10(-8) or 10(-9) M) was started simultaneously with high glucose (16.7 mM), only the second phase of insulin release was suppressed (P less than 0.05). Galanin (10(-9) M) failed to inhibit insulin release stimulated by L-arginine (10 and 5 mM) or potassium (25 and 20 mM). These findings suggest that the inhibitory action of galanin on glucose-stimulated insulin release is exerted on early intracellular events that occur during the stimulation of insulin release and that are common to both phases. Because galanin does not inhibit insulin release stimulated by L-arginine or potassium, galanin may inhibit glucose-stimulated closure of potassium channels.

scholarly journals Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800
Author(s):  
Jung-Taek Kwon ◽  
Mimi Lee ◽  
Gun-Baek Seo ◽  
Hyun-Mi Kim ◽  
Ilseob Shim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Lung Epithelial Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Lung Epithelial ◽  
Dose Dependent ◽  
A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

scholarly journals Biphasic Dose–Response Induced by PCB150 and PCB180 in HeLa Cells and Potential Molecular Mechanisms

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091004
Author(s):  
Ainy Zehra ◽  
Muhammad Zaffar Hashmi ◽  
Abdul Majid Khan ◽  
Tariq Malik ◽  
Zaigham Abbas
Keyword(s):  
Hela Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Genotoxic Effects ◽  
Species Formation ◽  
Low Concentrations ◽  
Extracellular Signal ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent

The polychlorinated biphenyls (PCBs) are persistent and their dose-dependent toxicities studies are not well-established. In this study, cytotoxic and genotoxic effects of PCB150 and PCB180 in HeLa cells were studied. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the cell proliferation was stimulated at low doses (10−3 and 10−2 µg/mL for 12, 24, 48, and 72 hours) and inhibited at high doses (10 and 15 µg/mL for 24, 48, and 72 hours) for both PCBs. Increase in reactive oxygen species formation was observed in the HeLa cells in a time- and dose-dependent manner. Malondialdehyde and superoxide dismutase showed increased levels at high concentrations of PCBs over the time. Glutathione peroxidase expression was downregulated after PCBs exposure, suggested that both PCB congeners may attributable to cytotoxicity. Comet assay elicited a significant increase in genotoxicity at high concentrations of PCBs as compared to low concentrations indicating genotoxic effects. PCB150 and PCB180 showed decrease in the activity of extracellular signal–regulated kinase 1/2 and c-Jun N-terminal kinase at high concentrations after 12 and 48 hours. These findings may contribute to understanding the mechanism of PCBs-induced toxicity, thereby improving the risk assessment of toxic compounds in humans.

Effects of Stearic Acid on Proliferation, Differentiation, Apoptosis, and Autophagy in Porcine Intestinal Epithelial Cells

2020 ◽  
Vol 20 (2) ◽  
pp. 157-166
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Stearic Acid ◽  
Er Stress ◽  
Intestinal Epithelial Cells ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent

Background: Stearic acid (SA), a saturated long-chain fatty acid consisting of 18 carbon atoms, is widely found in feed ingredients, such as corn, soybeans, and wheat. However, the roles of SA in the renewal of intestinal epithelial cells remain unclear. Methods and Results: In the present study, we found that 0.01-0.1 mM SA promoted IPEC-J2 cell differentiation and did not affect IPEC-J2 cell viability. In addition, the results showed that the viability of IPEC-J2 cells was inhibited by SA in a time- and dose-dependent manner at high concentrations. Flow cytometry and western blot analysis suggested that SA induced apoptosis, autophagy and ER stress in cells. In addition, the amounts of triglyceride were significantly increased upon challenge with SA. Moreover, the decrease in the viability of cells induced by SA could be attenuated by 4-PBA, an inhibitor of ER stress. Conclusion: In summary, SA accelerated IPEC-J2 cell differentiation at 0.01-0.1 mM. Furthermore, SA induced IPEC-J2 cell apoptosis and autophagy by causing ER stress.

scholarly journals Nucleoside uptake in rat liver parenchymal cells

1996 ◽  
Vol 317 (3) ◽  
pp. 835-842 ◽  
Author(s):  
Joan MERCADER ◽  
Mireia GOMEZ-ANGELATS ◽  
Belén del SANTO ◽  
Javier CASADO ◽  
Antonio F. FELIPE ◽  
...  
Keyword(s):  
Rat Liver ◽  
Nucleoside Transport ◽  
Transport Systems ◽  
Dependent Manner ◽  
Transport Activity ◽  
Liver Parenchymal ◽  
Uridine Uptake ◽  
High Concentrations ◽  
Parenchymal Cells ◽  
Dose Dependent

Rat liver parenchymal cells express Na+-dependent and Na+-independent nucleoside transport activity. The Na+-dependent component shows kinetic properties and substrate specificity similar to those reported for plasma membrane vesicles [Ruiz-Montasell, Casado, Felipe and Pastor-Anglada (1992) J. Membr. Biol. 128, 227–233]. This transport activity shows apparent Km values for uridine in the range 8–13 μM and a Vmax of 246 pmol of uridine per 3 min per 106 cells. Most nucleosides, including the analogue formycin B, cis-inhibit Na+-dependent uridine transport, although thymidine and cytidine are poor inhibitors. Inosine and adenosine inhibit Na+-dependent uridine uptake in a dose-dependent manner, reaching total inhibition. Guanosine also inhibits Na+-dependent uridine uptake, although there is some residual transport activity (35% of the control values) that is resistant to high concentrations of guanosine but may be inhibited by low concentrations of adenosine. The transport activity that is inhibited by high concentrations of thymidine is similar to the guanosine-resistant fraction. These observations are consistent with the presence of at least two Na+-dependent transport systems. Na+-dependent uridine uptake is sensitive to N-ethylmaleimide treatment, but Na+-independent transport is not. Nitrobenzylthioinosine (NBTI) stimulates Na+-dependent uridine uptake. The NBTI effect involves a change in Vmax, it is rapid, dose-dependent, does not need preincubation and can be abolished by depleting the Na+ transmembrane electrochemical gradient. Na+-independent uridine transport seems to be insensitive to NBTI. Under the same experimental conditions, NBTI effectively blocks most of the Na+-independent uridine uptake in hepatoma cells. Thus the stimulatory effect of NBTI on the concentrative nucleoside transporter of liver parenchymal cells cannot be explained by inhibition of nucleoside efflux.

scholarly journals Silver Nanoparticles Decrease the Viability of Cryptosporidium parvum Oocysts

2015 ◽  
Vol 82 (2) ◽  
pp. 431-437 ◽  
Author(s):  
Pamela Cameron ◽  
Birgit K. Gaiser ◽  
Bidha Bhandari ◽  
Paul M. Bartley ◽  
Frank Katzer ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cryptosporidium Parvum ◽  
Silver Ions ◽  
Protozoan Parasite ◽  
Dependent Manner ◽  
Oocyst Wall ◽  
Content Type ◽  
Chlorine Disinfection ◽  
High Concentrations ◽  
Dose Dependent

ABSTRACTOocysts of the waterborne protozoan parasiteCryptosporidium parvumare highly resistant to chlorine disinfection. We show here that both silver nanoparticles (AgNPs) and silver ions significantly decrease oocyst viability, in a dose-dependent manner, between concentrations of 0.005 and 500 μg/ml, as assessed by an excystation assay and the shell/sporozoite ratio. For percent excystation, the results are statistically significant for 500 μg/ml of AgNPs, with reductions from 83% for the control to 33% with AgNPs. For Ag ions, the results were statistically significant at 500 and 5,000 μg/ml, but the percent excystation values were reduced only to 66 and 62%, respectively, from 86% for the control. The sporozoite/shell ratio was affected to a greater extent following AgNP exposure, presumably because sporozoites are destroyed by interaction with NPs. We also demonstrated via hyperspectral imaging that there is a dual mode of interaction, with Ag ions entering the oocyst and destroying the sporozoites while AgNPs interact with the cell wall and, at high concentrations, are able to fully break the oocyst wall.

scholarly journals Modulation of electrical activity and ionic currents of isolated neurons by orexin A

2013 ◽  
Vol 11 (4) ◽  
pp. 54-60
Author(s):  
Petr Dmitriyevich Shabanov ◽  
Anatoliy Ivanovich Vislobokov
Keyword(s):  
Membrane Potential ◽  
Lymnaea Stagnalis ◽  
Ionic Currents ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Isolated Neurons ◽  
Orexin A ◽  
High Concentrations ◽  
Kinetics Of ◽  
Dose Dependent

The changes in intracellular potential of resting (PR) and potential of action (PA) of the identified neurons of pedal and visceral ganglia of the CNS mollusk Planorbarius corneus registered by means of intracellular electrodes, and ionic currents of isolated neurons under fixed potential after administration of orexin A in concentrations 1, 10, 100 and 1000 µg/ml were studied by the method of fixation of membrane potential in isolated neurons of the Lymnaea stagnalis mollusk. Dibazol in concentrations of 1 and 10 µM effected slightly on the ionic currents. High concentrations of dibazol (100 and 1000 µM) inhibited all currents in dose dependent manner with maximal effect on potassium currents amplitude. ЕС50 were 7.4 мМ for INa, 4.0 мМ for ICa, 83.9 µM for IKs,1 (one group of neurons) and 2.9 мМ for IKs,2 (the another group of neurons). The voltage-amper membrane characteristics shift was not registered, but the kinetics of currents development was changed. Dibazol was more effective in inhibition of ionic currents compared to its structural analogs.

scholarly journals Dehydroepiandrosterone Reduced Lipid Droplet Accumulation via Inhibiting Cell Proliferation and Improving Mitochondrial Function in Primary Chicken Hepatocytes

2018 ◽  
pp. 443-456
Author(s):  
L.-L. LI ◽  
D. WANG ◽  
C.-Y. GE ◽  
L. YU ◽  
J.-L. ZHAO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lipid Droplet ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Lipid Droplets ◽  
Dependent Manner ◽  
Mitochondrial Membrane Permeability ◽  
Cyclin Dependent Kinases ◽  
Dhea Treatment ◽  
Dose Dependent

Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes.

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