A broad spectrum anticancer nucleoside with selective toxicity against human colon cells in vitro

Background and objectives: Arabinoxylans (AX) can gel and exhibit antioxidant capacity. Previous studies have demonstrated the potential application of AX microspheres as colon-targeted drug carriers. However, the cytotoxicity of AX gels has not been investigated so far. Therefore, the aim of the present study was to prepare AX-based particles (AXM) by coaxial electrospraying method and to investigate their antioxidant potential and cytotoxicity on human colon cells. Materials and Methods: The gelation of AX was studied by monitoring the storage (G′) and loss (G′′) moduli. The morphology of AXM was evaluated using optical and scanning electron microscopy (SEM). The in vitro antioxidant activity of AX before and after gelation was measured using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. In addition, the effect of AX and AXM on the proliferation of human colon cells (CCD 841 CoN) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The final G′ and G′′ values for AX gels were 293 and 0.31 Pa, respectively. AXM presented spherical shape and rough surface with a three-dimensional and porous network. The swelling ratio and mesh size of AXM were 35 g water/g AX and 27 nm, respectively. Gelation decreased the antioxidant activity of AX by 61–64 %. AX and AXM did not affect proliferation or show any toxic effect on the normal human colon cell line CCD 841 CoN. Conclusion: The results indicate that AXM could be promising biocompatible materials with antioxidant activity.

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Mismatch Repair Proteins Are Activators of Toxic Responses to Chromium-DNA Damage

Molecular and Cellular Biology ◽

10.1128/mcb.25.9.3596-3607.2005 ◽

2005 ◽

Vol 25 (9) ◽

pp. 3596-3607 ◽

Cited By ~ 78

Author(s):

Elizabeth Peterson-Roth ◽

Mindy Reynolds ◽

George Quievryn ◽

Anatoly Zhitkovich

Keyword(s):

Dna Damage ◽

Mismatch Repair ◽

Dna Adducts ◽

Human Colon ◽

Repair System ◽

Very High Frequency ◽

Colon Cells ◽

Lung Cancers ◽

Toxic Responses

ABSTRACT Chromium(VI) is a toxic and carcinogenic metal that causes the formation of DNA phosphate-based adducts. Cr-DNA adducts are genotoxic in human cells, although they do not block replication in vitro. Here, we report that induction of cytotoxicity in Cr(VI)-treated human colon cells and mouse embryonic fibroblasts requires the presence of all major mismatch repair (MMR) proteins. Cr-DNA adducts lost their ability to block replication of Cr-modified plasmids in human colon cells lacking MLH1 protein. The presence of functional mismatch repair caused induction of p53-independent apoptosis associated with activation of caspases 2 and 7. Processing of Cr-DNA damage by mismatch repair resulted in the extensive formation of γ-H2AX foci in G2 phase, indicating generation of double-stranded breaks as secondary toxic lesions. Induction of γ-H2AX foci was observed at 6 to 12 h postexposure, which was followed by activation of apoptosis in the absence of significant G2 arrest. Our results demonstrate that mismatch repair system triggers toxic responses to Cr-DNA backbone modifications through stress mechanisms that are significantly different from those for other forms of DNA damage. Selection for Cr(VI) resistant, MMR-deficient cells may explain the very high frequency of lung cancers with microsatellite instability among chromate workers.

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Effect of Roasting and Alkalization on the Chemical Composition and In Vitro Anti-Inflammatory Effects of Cocoa

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_054 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 421-421

Author(s):

Joshua Lambert ◽

Talia Seymore ◽

Qiaoqiao Dai ◽

Gregory Ziegler

Keyword(s):

Chemical Composition ◽

Human Colon ◽

Sensory Characteristics ◽

Inflammatory Activity ◽

Total Phenolic ◽

Cocoa Beans ◽

Inhibitory Potency ◽

Colon Cells ◽

Anti Inflammatory

Abstract Objectives Cocoa beans undergo fermentation, roasting, and possibly alkalization prior to consumption. Cocoa and chocolate have been shown to exert anti-inflammatory effects. Previous studies have shown that roasting and alkalization can adversely affect the total phenolic content (TPC) of cocoa, but the effect of these steps on bioactivity has not been well-studied. Our objective was to prepare cocoa powders using different roasting and alkalization protocols and measure their chemical composition and in vitro anti-inflammatory activity. Methods Cocoa beans were roasted (110–150°C) and alkali-treated (0 – 120 min) using a 22 + center point study design. Cocoa nibs were defatted and extracted with 70% aqueous acetone. The extract was dried prior to analysis. TPC was determined using the Folin-Ciocalteu method. Select polyphenols were quantified by liquid chromatography. In vitro anti-inflammatory activity was assessed as inhibition of phospholipase A2 (PLA2) and inhibition of interleukin 8 (IL8) production by tumor necrosis factor a-stimulated HT-29 human colon cells. Results Roasting and alkalization led to decreased TPC, but alkalization had a greater effect. Cocoa beans roasted at 130°C and alkalized for 120 min had 44% lower TPC than those roasted that same way but without alkalization. In the absence of alkalization, beans roasted at 150°C had only a 13% lower TPC than beans roasted at 110°C. Roasting and alkalization also influenced the levels of individual polyphenols, but the effects varied based on the analyte of interest. Roasting tended to enhance the PLA2, inhibitory potency of the cocoa whereas alkalization reduced inhibitory potency. Cocoa that had been roasted at 150°C but not alkalized had the lowest IC50 (14 mg/mL) whereas cocoa that had been roasted at 150°C and alkalized for 120 min had the highest (>100 mg/mL). Similar results were observed for inhibition of IL8 production. Conclusions Roasting and alkalization are important for achieving desired sensory characteristics in cocoa, but these processes adversely affect the levels of polyphenols in cocoa and has been considered inconsistent with maintaining bioactivity. Our results suggest that it is possible to identify processing protocols that balance the sensory characteristics of cocoa with its anti-inflammatory activity. Funding Sources This work was funded by USDA AFRI.

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Gastrointestinal digested Sambucus nigra L. fruit extract protects in vitro cultured human colon cells against oxidative stress

Food Chemistry ◽

10.1016/j.foodchem.2015.11.017 ◽

2016 ◽

Vol 197 ◽

pp. 648-657 ◽

Cited By ~ 23

Author(s):

Anna Olejnik ◽

Mariola Olkowicz ◽

Katarzyna Kowalska ◽

Joanna Rychlik ◽

Radosław Dembczyński ◽

...

Keyword(s):

Oxidative Stress ◽

Human Colon ◽

Sambucus Nigra ◽

Fruit Extract ◽

Colon Cells

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IN VITRO STUDIES OF ULCERATIVE COLITIS

Journal of Experimental Medicine ◽

10.1084/jem.117.5.705 ◽

1963 ◽

Vol 117 (5) ◽

pp. 705-716 ◽

Cited By ~ 78

Author(s):

Ove Broberger ◽

Peter Perlmann

Keyword(s):

Ulcerative Colitis ◽

Tissue Culture ◽

Guinea Pig ◽

Human Colon ◽

Final Concentration ◽

Cytotoxic Action ◽

Colon Cells ◽

Negative Results ◽

Pig Serum

By means of immunofluorescent methods it has been shown that sera from children with ulcerative colitis contain antibodies which react with fetal colon cells in tissue culture. 5 out of 13 sera from patients reacted positively when tested for staining antibodies while 12 sera from healthy individuals yielded negative results. The specificity of the staining reactions was confirmed by inhibition experiments. The staining capacity of various sera was correlated to their hemagglutinating titer when tested against phenol-water extracts of human colon. The presence of blood group substances of the ABO system on fetal colon cells in tissue culture could be demonstrated by application of fluorescent H agglutinins from eel. Cross-inhibition experiments indicated that the H agglutinins stained colon antigens which were different from those reacting with the antibodies of ulcerative colitis sera. The reactivity of cultured fetal colon cells with the antibodies in ulcerative colitis sera was retained for up to 12 days, with optimal staining at 4 to 5 days. Reactivity with H agglutinins was present for a longer period, sometimes more than 20 days. Although antigen could be shown to be present on fetal colon cells in tissue culture, exposure of the culture, in the presence of fresh guinea pig serum, to sera from patients with ulcerative colitis did not lead to any visible cytotoxic damage. In order to investigate the possible cytotoxic effect of the sera with a more sensitive technique, freshly explanted fetal colon was dispersed by trypsinization and the cells labeled with 32P-orthophosphate. Subsequently, these cells were exposed to sera, in a final concentration of 30 per cent, from patients or healthy controls in the presence of fresh guinea pig serum (final concentration 15 per cent). Approximately 20 per cent of the cellular isotope was released into the medium within 150 minutes of incubation, but the release was the same in the samples treated either with patients' sera or normal control sera. Thus, under the present conditions, the patients' sera did not exert any specific cytotoxic action on colon cells.

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Toxicity of Volatile Methylated Species of Bismuth, Arsenic, Tin, and Mercury in Mammalian CellsIn Vitro

Journal of Toxicology ◽

10.1155/2011/503576 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

E. Dopp ◽

U. von Recklinghausen ◽

J. Hippler ◽

R. A. Diaz-Bone ◽

J. Richard ◽

...

Keyword(s):

Cell Lines ◽

Mammalian Cells ◽

Human Colon ◽

Cell Type ◽

Hep G2 ◽

Colon Cells ◽

Toxic Compound ◽

Low Concentrations ◽

Low Toxicity

The biochemical transformation of mercury, tin, arsenic and bismuth through formation of volatile alkylated species performs a fundamental role in determining the environmental processing of these elements. While the toxicity of inorganic forms of most of these compounds are well documented (e.g., arsenic, mercury) and some of them are of relatively low toxicity (e.g., tin, bismuth), the more lipid-soluble organometals can be highly toxic. In the present study we investigated the cyto- and genotoxicity of five volatile metal(loid) compounds: trimethylbismuth, dimethylarsenic iodide, trimethylarsine, tetramethyltin, and dimethylmercury. As far as we know, this is the first study investigating the toxicity of volatile metal(loid) compoundsin vitro. Our results showed that dimethylmercury was most toxic to all three used cell lines (CHO-9 cells, CaCo, Hep-G2) followed by dimethylarsenic iodide. Tetramethyltin was the least toxic compound; however, the toxicity was also dependend upon the cell type. Human colon cells (CaCo) were most susceptible to the toxicity of the volatile compounds compared to the other cell lines. We conclude from our study that volatile metal(loid) compounds can be toxic to mammalian cells already at very low concentrations but the toxicity depends upon the metal(loid) species and the exposed cell type.

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Molecules Present in Plant Essential Oils for Prevention and Treatment of Colorectal Cancer (CRC)

Molecules ◽

10.3390/molecules26040885 ◽

2021 ◽

Vol 26 (4) ◽

pp. 885

Author(s):

Giovannamaria Petrocelli ◽

Fulvia Farabegoli ◽

Maria Chiara Valerii ◽

Catia Giovannini ◽

Alberto Sardo ◽

...

Keyword(s):

Colorectal Cancer ◽

Essential Oils ◽

Cell Line ◽

Targeted Delivery ◽

Complex Mixture ◽

Human Colon ◽

Epithelial Cell Line ◽

Colon Cells ◽

Anticancer Properties

Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, commonly present in the human diet. In recent years, many in vitro studies have suggested possible anticancer properties of single EO compounds, on colorectal cancer (CRC) cells. However, the majority of these studies did not compare the effects of these compounds on normal and cancer colon cells. By using NCM-460, a normal human mucosal epithelial cell line, Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from lymph node metastatic site, we identified cinnamaldehyde, derived from cinnamon EO and eugenol, derived from bud clove EO, as compounds with a specific anticancer action selectively targeting the transformed colonic cells. Both cinnamaldehyde (75 µM) and eugenol (800 µM), after 72 h of treatment, were capable to induce apoptosis, necrosis and a cell cycle slowdown in Caco-2 and in SW-620, but not in NCM-460 cells. If associated with a targeted delivery to the colon, these two compounds could prove effective in the prevention or treatment of CRC.

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Chemopreventive effects of in vitro digested and fermented bread in human colon cells

European Journal of Nutrition ◽

10.1007/s00394-011-0262-8 ◽

2011 ◽

Vol 51 (7) ◽

pp. 827-839 ◽

Cited By ~ 18

Author(s):

Wiebke Schlörmann ◽

Beate Hiller ◽

Franziska Jahns ◽

Romy Zöger ◽

Isabell Hennemeier ◽

...

Keyword(s):

Human Colon ◽

Colon Cells

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Bioactivity of Juniperus communis essential oil and post-distillation waste: Assessment of selective toxicity against food contaminants

Archives of Biological Sciences ◽

10.2298/abs181217005n ◽

2019 ◽

Vol 71 (2) ◽

pp. 235-244 ◽

Cited By ~ 7

Author(s):

Biljana Nikolic ◽

Bojana Vasilijevic ◽

Ana Ciric ◽

Dragana Mitic-Culafic ◽

Stefana Cvetkovic ◽

...

Keyword(s):

Essential Oil ◽

Antimicrobial Effect ◽

Food Spoilage ◽

Food Contaminants ◽

Selective Toxicity ◽

Colon Cells ◽

Juniperus Communis ◽

Minimum Fungicidal Concentration ◽

In Vitro Adhesion

Previously chemically characterized Juniperus communis essential oil (EO) and post-distillation waste (PDW) were tested for cytotoxicity and antimicrobial activity against food contaminants. Microdilution assay showed that PDW induced moderate antifungal (minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values, ranging between 0.118-0.900 mg mL-1), and an antibacterial effect against Listeria monocytogenes (MIC and minimum bactericidal concentration (MBC) were 0.39 and 0.74 mg mL-1, respectively). Combinations of EO/PDW with selected antibiotics induced synergistic antilisterial activity in the checkerboard assay. The MTT assay determined that cytotoxicity against colon cancer cells was high for the EO but negligible for PDW (IC50 values were 0.087-0.106 and 1.450-6.840 mg mL-1, respectively). The selectivity indices indicated high selectivity of PDW against tested fungi and L. monocytogenes. In the adhesion-inhibition assay, PDW reduced in vitro adhesion of L. monocytogenes to colon cells (29-62% of inhibition). In conclusion, PDW exhibited an antimicrobial effect against important food spoilage and poisoning fungi and L. monocytogenes, and also reduced in vitro adhesion of L. monocytogenes to colon cells. The results indicate that J. communis PDW could be considered as natural preservative against food spoilage and poisonous fungi, and as an adjuvant to conventional therapy of listeriosis.

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