scholarly journals Protopine/Gemcitabine Combination Induces Cytotoxic or Cytoprotective Effects in Cell Type-Specific and Dose-Dependent Manner on Human Cancer and Normal Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 90
Author(s):  
Mercedes Garcia-Gil ◽  
Benedetta Turri ◽  
Morena Gabriele ◽  
Laura Pucci ◽  
Alessandro Agnarelli ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Human Tumor ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Cell Type ◽  
Mitochondrial Ros ◽  
Cell Type Specific ◽  
Natural Alkaloid ◽  
Dose Dependent

The natural alkaloid protopine (PRO) exhibits pharmacological properties including anticancer activity. We investigated the effects of PRO, alone and in combination with the chemotherapeutic gemcitabine (GEM), on human tumor cell lines and non-tumor human dermal fibroblasts (HDFs). We found that treatments with different PRO/GEM combinations were cytotoxic or cytoprotective, depending on concentration and cell type. PRO/GEM decreased viability in pancreatic cancer MIA PaCa-2 and PANC-1 cells, while it rescued the GEM-induced viability decline in HDFs and in tumor MCF-7 cells. Moreover, PRO/GEM decreased G1, S and G2/M phases, concomitantly with an increase of subG1 phase in MIA PaCa-2 and PANC-1 cells. Differently, PRO/GEM restored the normal progression of the cell cycle, altered by GEM, and decreased cell death in HDFs. PRO alone increased mitochondrial reactive oxygen species (ROS) in MIA PaCa-2, PANC-1 cells and HDFs, while PRO/GEM increased both intracellular and mitochondrial ROS in the three cell lines. These results indicate that specific combinations of PRO/GEM may be used to induce cytotoxic effects in pancreatic tumor MIA PaCa-2 and PANC-1 cells, but have cytoprotective or no effects in HDFs.

scholarly journals Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner

2005 ◽  
Vol 86 (8) ◽  
pp. 2305-2314 ◽  
Author(s):  
Marian Wiegand ◽  
Sascha Bossow ◽  
Wolfgang J. Neubert
Keyword(s):  
Cell Lines ◽  
Cytopathic Effect ◽  
Sendai Virus ◽  
Cellular Protein ◽  
Dependent Manner ◽  
Cell Type ◽  
Initiator Caspases ◽  
A Cell ◽  
Cell Type Specific ◽  
Intracellular Antigen

Induction of apoptosis during Sendai virus (SeV) infection has previously been documented to be triggered by initiator caspases (for strain F) or by a contribution of the cellular protein TIAR (T-cell-activated intracellular antigen-related) (for strain Z). Here, evidence was provided that both TIAR and caspases are simultaneously involved in apoptosis induction as a result of infection with SeV strain F. SeV F infection induced death in all tested cell lines, which could only be partially prevented through the pan-caspase inhibitor z-VAD-fmk. However, infection of seven different cell lines with the SeV mutant Fctr48z overexpressing a TIAR-sequestering RNA from the modified leader resulted in a cell type-dependent reduced cytopathic effect (CPE); in an earlier study a similar mutant derived from SeV Z was shown to prevent the induction of any CPE. Finally, blocking of caspases through z-VAD-fmk combined with Fctr48z infection led to complete abrogation of CPE, clearly demonstrating the existence of two separate mechanisms inducing cell death during SeV F infections. Interestingly, a cell type-specific interference between these two mechanisms could be detected during infection with the mutant virus Fctr48z: RNA transcribed from the mutated leader was able to trans-dominantly inhibit caspase-mediated apoptosis. Thus, virus-expressed factors enabling a well-balanced ratio of suppression and triggering of apoptosis seem to be essential for optimal virus replication.

scholarly journals Cytotoxic Effect on Cancer Cells and Structural Identification of Phenols from Spatholobi Caulis by HPLC-ESI-MSn

2009 ◽  
Vol 4 (6) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Dan Lu ◽  
Hua He ◽  
Bin Wu ◽  
Shanjing Yao
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Screening Tests ◽  
Hl60 Cell ◽  
Dependent Manner ◽  
Dose Dependent

To find fractions from Spatholobi caulis with cytotoxic effects on cancer cell lines, screening tests were carried out using the SRB assay on the HL60 cell line. Further investigation with HL60 and another four human cancer cell lines (KB, K562, MCF-7 and Hep G2), revealed a dose-dependent response. High-performance liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (HPLC- ESI-MSn) was used to isolate and identify the active constituents from the active fraction. Three fractions (F-IV, F-V and F-VII) showed in vitro cytotoxicity. F-V inhibited the growth of cancer cells in a dose-dependent manner. The IC50 values for KB, K562 and HL60 cells were 17.6, 8.3 and 9.7 μg/mL, respectively. The dominating constituents of F-V were either identified or tentatively characterized as nine phenolic compounds, eight isoflavones and 9-methoxycoumestrol. The isoflavones 7-hydroxy-3′,4′-dimethoxy isoflavone, 7-hydroxy-6,2′,4′-trimethoxy isoflavone and 3′-hydroxy-7,4′-dimethoxy isoflavone are reported for the first time for Spatholobi caulis. The results suggest that these compounds contribute to the cytotoxic effect of Spatholobi caulis.

scholarly journals Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Loaded with Carboplatin Enhance Cytotoxicity on Human Cancer Cell Lines

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3622
Author(s):  
César Adrián Leyva-González ◽  
Daniel Salas-Treviño ◽  
Flavio Fernando Contreras-Torres ◽  
María de Jesús Loera-Arias ◽  
Christian Alexis Gómez-Tristán ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Cell Lines ◽  
Human Cancer ◽  
Human Tumor ◽  
Public Health Problem ◽  
Mammary Adenocarcinoma ◽  
Dependent Manner ◽  
Global Public Health ◽  
Multiple Cancer

Cancer is a major global public health problem and conventional chemotherapy has several adverse effects and deficiencies. As a valuable option for chemotherapy, nanomedicine requires novel agents to increase the effects of antineoplastic drugs in multiple cancer models. Since its discovery, carbon nanotubes (CNTs) are intensively investigated for their use as carriers in drug delivery applications. This study shows the development of a nanovector generated with commercial carbon nanotubes (cCNTs) that were oxidized (oxCNTs) and chemically functionalized with hyaluronic acid (HA) and loaded with carboplatin (CPT). The nanovector, oxCNTs–HA–CPT, was used as a treatment against HeLa and MDA–MB-231 human tumor cell lines. The potential antineoplastic impact of the fabricated nanovector was evaluated in human cervical adenocarcinoma (HeLa) and mammary adenocarcinoma (MDA-MB-231). The oxCNTs–HA–CPT nanovector demonstrate to have a specific antitumor effect in vitro. The functionalization with HA allows that nanovector bio–directed towards tumor cells, while the toxicity effect is attributed mainly to CPT in a dose-dependent manner.

scholarly journals Cytotoxicity of Cyclodipeptides fromPseudomonas aeruginosaPAO1 Leads to Apoptosis in Human Cancer Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Dolores Vázquez-Rivera ◽  
Omar González ◽  
Jaquelina Guzmán-Rodríguez ◽  
Alma L. Díaz-Pérez ◽  
Alejandra Ochoa-Zarzosa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Flow Cytometric Analysis ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Human Cancer Cell ◽  
Apoptotic Pathway ◽  
Human Cancer Cell Lines

Pseudomonas aeruginosais an opportunistic pathogen of plants and animals, which produces virulence factors in order to infect or colonize its eukaryotic hosts. Cyclodipeptides (CDPs) produced byP. aeruginosaexhibit cytotoxic properties toward human tumor cells. In this study, we evaluated the effect of a CDP mix, comprised of cyclo(L-Pro-L-Tyr), cyclo(L-Pro-L-Val), and cyclo(L-Pro-L-Phe) that were isolated fromP. aeruginosa, on two human cancer cell lines. Our results demonstrated that the CDP mix promoted cell death in cultures of the HeLa cervical adenocarcinoma and Caco-2 colorectal adenocarcinoma cell lines in a dose-dependent manner, with a 50% inhibitory concentration (IC50) of 0.53 and 0.66 mg/mL, for HeLa and Caco-2 cells, respectively. Flow cytometric analysis, using annexin V and propidium iodide as apoptosis and necrosis indicators, respectively, clearly showed that HeLa and Caco-2 cells exhibited apoptotic characteristics when treated with the CDP mix at a concentration <0.001 mg/mL. IC50values for apoptotic cells in HeLa and Caco-2 cells were 6.5 × 10−5and 1.8 × 10−4 mg/mL, respectively. Our results indicate that an apoptotic pathway is involved in the inhibition of cell proliferation caused by theP. aeruginosaCDP mix.

scholarly journals Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1156
Author(s):  
Madelaine Sugasti-Salazar ◽  
Yessica Y. Llamas-González ◽  
Dalkiria Campos ◽  
José González-Santamaría
Keyword(s):  
Protein Expression ◽  
Hela Cells ◽  
Plaque Assay ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Mitogen Activated Protein ◽  
Mayaro Virus ◽  
The Impact ◽  
Dose Dependent

Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

Cytometric Profiling of CD133+ Cells in Human Colon Carcinoma Cell Lines Identifies a Common core Phenotype and Cell Type-specific Mosaics

2013 ◽  
Vol 28 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Marica Gemei ◽  
Rosa Di Noto ◽  
Peppino Mirabelli ◽  
Luigi Del Vecchio
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Cell Type ◽  
Carcinoma Cell Lines ◽  
Cell Type Specific

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.

scholarly journals New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 974
Author(s):  
César Díaz-Godínez ◽  
Joshue Fabián Jorge-Rosas ◽  
Mario Néquiz ◽  
Santiago Martínez-Calvillo ◽  
Juan P. Laclette ◽  
...  
Keyword(s):  
Cell Surface ◽  
Nadph Oxidase ◽  
Entamoeba Histolytica ◽  
Pathogen Detection ◽  
Dependent Manner ◽  
Antimicrobial Proteins ◽  
Nadph Oxidase Activity ◽  
Mitochondrial Ros ◽  
Pre Treatment ◽  
Dose Dependent

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additionally, we detected the presence of MPO on the cell surface of trophozoites after the interaction with neutrophils and found that luminol and isoluminol, intracellular and extracellular scavengers for MPO derived ROS reduced the amount of NET triggered by amoebas. These data suggest that ROS generated by trophozoites and processed by the extracellular MPO during the contact with neutrophils are required for E. histolytica induced NETosis.

scholarly journals CYTOTOXICITY ACTIVITY OF SOME INDIAN MEDICINAL PLANTS

2016 ◽  
Vol 8 (4) ◽  
pp. 86
Author(s):  
Dora Babu Neerugatti ◽  
Ganga Rao Battu ◽  
Raviteja Bandla
Keyword(s):  
Medicinal Plants ◽  
Cell Lines ◽  
Human Cancer ◽  
Bioactive Constituents ◽  
Cytotoxicity Activity ◽  
Human Cancer Cell Lines ◽  
Methanolic Extracts ◽  
Dose Dependent ◽  
New Anticancer Drugs ◽  
Indian Medicinal Plants

Objective: The current study is carried out to evaluate cytotoxicity activity of the methanolic extracts of some medicinal plants (Buchanania axillaris Desr, Tamilnadia ulignosa Retz, Phaseolus semierectus L and Stylosanthes fruticosa Retz).Methods: Cytotoxicity activity was evaluated on human cancer cell lines such as lung cancer (A549) and skin cancer (A431) using MTT assay method.Results: The selected plant extracts showed the dose-dependent cytotoxicity activity on the tested cell lines. The cytotoxicity variations on different cell lines were also observed for tested plants extracts. The cytotoxicity of the extracts was increased as the concentration of them was increased. Among all tested plants extracts Phaseolus semierectus showed the better cytotoxicity activity on tested cell lines.Conclusion: The results of the present study supported the folkloric usage of the studied plants and confirmed that the plant's extracts have the bioactive constituents with cytotoxic properties and their isolation can be useful for developing new anticancer drugs.

scholarly journals Genetic engineering for in vivo optical interrogation of neuronal responses to cell type-specific silencing

2021 ◽  
Author(s):  
Firat Terzi ◽  
Johannes Knabbe ◽  
Sidney B. Cambridge
Keyword(s):  
High Resolution ◽  
Genetic Engineering ◽  
Transgene Expression ◽  
Neuronal Morphology ◽  
Dependent Manner ◽  
Cell Type ◽  
Fluorescent Marker ◽  
Genetic Perturbations ◽  
Cell Type Specific

SummaryGenetic engineering of quintuple transgenic brain tissue was used to establish a low background, Cre-dependent version of the inducible Tet-On system for fast, cell type-specific transgene expression in vivo. Co-expression of a constitutive, Cre-dependent fluorescent marker selectively allowed single cell analyses before and after inducible, tet-dependent transgene expression. Here, we used this method for acute, high-resolution manipulation of neuronal activity in the living brain. Single induction of the potassium channel Kir2.1 produced cell type-specific silencing within hours that lasted for at least three days. Longitudinal in vivo imaging of spontaneous calcium transients and neuronal morphology demonstrated that prolonged silencing did not alter spine densities or synaptic input strength. Furthermore, selective induction of Kir2.1 in parvalbumin interneurons increased the activity of surrounding neurons in a distance-dependent manner. This high-resolution, inducible interference and interval imaging of individual cells (high I5, ‘HighFive’) method thus allows visualizing temporally precise, genetic perturbations of defined cells.

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