Delphinidin protects colon carcinoma cells against the genotoxic effects of the mycotoxin altertoxin II

Aichinger, Georg; Puntscher, Hannes; Beisl, Julia; Kütt, Mary-Liis; Warth, Benedikt; Marko, Doris

doi:10.1016/j.toxlet.2017.12.002

Cited by 39 publications

(42 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the stronger response elicited by H 2 O 2 challenge after incubation of HCEC with ATXII in comparison to HT-29 sustains the interpretation that the membrane of the non-transformed cells could be more sensitive, and consequently, the barrier function of the epithelial cells more fragile. Due to the presence of an epoxide group at the perylene quinone scaffold, ATXII is known to be a relatively reactive compound (Aichinger et al 2018; Fleck et al 2014a). In this light, it is prone not only to the activation of the Nrf2/ARE pathway (Jarolim et al 2017), but also to direct reaction with diverse cell structures (Fleck et al 2012; Jarolim et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…However, data concerning its occurrence in food and feed are limited and great effort is continuously devoted to the development/optimization of analytical methods for its detection (Puntscher et al 2018; Zwickel et al 2016b). To add complexity to this scenario, actual data indicate that ATXII may promptly react with food constituents (Aichinger et al 2018). The fate of ATXII during food production is still unknown and currently subject to intensive research, thus still hampering any reliable exposure estimation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Functional impairment triggered by altertoxin II (ATXII) in intestinal cells in vitro: cross-talk between cytotoxicity and mechanotransduction

2018

Self Cite

View full text Add to dashboard Cite

Intestinal cells are able to continuously integrate response to multiple stimuli/stressors; these include the concomitant activation of “chemically driven” pathways, of paramount importance in the response to toxicants, as well as physical stimulation derived from motility. Altertoxin II (ATXII, 0.1, 1 and 10 µM), a mycotoxin produced by the food contaminant fungus Alternaria alternata was studied in HT-29 intestinal adenocarcinoma cells and in non-transformed intestinal epithelial cells, HCEC. One-hour incubation with ATXII was sufficient to trigger irreversible cytotoxicity in both cell types, as well as to modify cellular responses to concomitant pro-oxidant challenge (H2O2, 100–500 µM, DCF-DA assay) suggesting that even relatively short-time exposure of the intestinal cells could be sufficient to alter their functionality. Combination of ATXII (1 µM) with physical stimulation typical of the intestinal compartment (shear stress) revealed differential response of tumor-derived epithelial cells HT-29 in comparison to HCEC, in particular in the localization of the transcription factor Nrf2 (NF-E2-related factor 2). Moreover, ATXII reduced the migratory potential of HCEC as well as their membrane fluidity, but had no respective impact on HT-29 cells. Taken together, ATXII appeared to alter predominantly membrane functionality in HCEC thus hampering crucial functions for cellular motility/turnover, as well as barrier function of healthy intestinal cells and had very limited activity on the tumor counterparts.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional impairment triggered by altertoxin II (ATXII) in intestinal cells in vitro: cross-talk between cytotoxicity and mechanotransduction

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Nalimov outlier test was applied to eliminate outliers. To assess interactions between the test compounds, a mathematical model, the "Independent Joint Action" by Webb (1963), was used whenever possible as previously published (Aichinger et al 2016(Aichinger et al , 2018b). An expected combined effect was calculated with the equation f ab = f a + f b − f a f b and compared to the measured combined effect using two-sample Student's t test.…”

Section: Discussionmentioning

confidence: 99%

Combinatory effects of cereulide and deoxynivalenol on in vitro cell viability and inflammation of human Caco-2 cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Deoxynivalenol (DON), one of the most abundant mycotoxins in cereal products, was recently detected with other mycotoxins and the emetic bacterial toxin cereulide (CER) in maize porridge. Within a cereal-based diet, co-exposure to these toxins is likely, hence raising the question of combinatory toxicological effects. While the toxicological evaluation of DON has quite progressed, consequences of chronic, low-dose CER exposure are still insufficiently explored. Information about the combinatory toxicological effects of these toxins is lacking. In the present study, we investigated how CER (0.1-100 ng/mL) and DON (0.01-10 µg/mL) alone and in a constant ratio of 1:100 (CER:DON) affect the cytotoxicity and immune response of differentiated human intestinal Caco-2 cells. While DON alone reduced cell viability only in the highest concentration (10 µg/mL), CER caused severe cytotoxicity upon prolonged incubation (starting from 10 ng/mL after 24 h and 48 h, 2.5 ng/ mL and higher after 72 h). After 72 h, synergistic effects were observed at 2.5 ng/mL CER and 0.25 µg/mL DON. Different endpoints of inflammation were investigated in interleukin-1β-stimulated Caco-2 cells. Notably, DON-induced interleukin-8 transcription and secretion were diminished by the presence of 10 and 25 ng/mL CER after short-term (5 h) incubation, indicating immunosuppressive properties. We hypothesise that habitual consumption of cereal-based foods co-contaminated with CER and DON may cause synergistic cytotoxic effects and an altered immune response in the human intestine. Therefore, further research concerning effects of co-occurring bacterial toxins and mycotoxins on the impairment of intestinal barrier integrity, intestinal inflammation and the promotion of malnutrition is needed.

show abstract

“…Soy isoflavones, genistein, and delphinidin were found to antagonize the genotoxic effects of AOH in a colon carcinoma cell line via influencing the generation of oxidative stress and poison topoisomerases (Aichinger, Beisl, & Marko, ). Delphinidin along with its degradation products phloroglucinol aldehyde and gallic acid seemed to protect colon cells against the genotoxic effects of ATX‐II through influencing the cellular antioxidant defense system and/or transporter proteins (Aichinger, Puntscher et al., Extracts of Eucalyptus globulus and Calendula officinalis may also induce a reduction of mycotoxins (TeA, AOH, and AME) (da Cruz Cabral, Fernández Pinto, & Patriarca, ).…”

Section: Food Compounds Especially Those Of Plant Origin For Prevenmentioning

confidence: 99%

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

Xue

Sun‐Waterhouse

Wang

et al. 2018

Comp Rev Food Sci Food Safe

View full text Add to dashboard Cite

Mycotoxins are contaminants commonly found in foods and represent a worldwide threat to human health and welfare. Efforts have been undertaken to reduce mycotoxins and their toxicity, including the introduction of good agricultural practices, appropriate food processing, specific biotransformation approaches, and pursue therapeutic agents to counteract mycotoxins. Efficient and predictive tools are required for investigations on mycotoxins and their toxicodynamics, and strategies for mycotoxin reduction. Gene expression and transcriptome analysis can unravel the mode of action, transformation and combined toxicity of mycotoxins, or mycotoxin's interactions with food components including dietary therapeutics, at the cellular level and from a molecular perspective. MicroRNAs (miRNAs) regulate endogenously and posttranscriptionally the expression of target genes and enzymes involved in physiological, disease and toxicological responses, and the metabolism of therapeutic agents. Accordingly, this review aimed to collect up‐to‐date information on (1) the regulatory role of miRNAs in mycotoxin‐initiated toxicological processes and (2) the protective role of active ingredients from plants on mycotoxin‐induced toxicity. Through such a review of published evidence, we found some common signal pathways involving miRNAs shared by these two types of biological events. This finding indicates the possibility of using miRNAs as biomarkers in assessing and controlling mycotoxins in food via cellular mechanisms.

show abstract

Delphinidin protects colon carcinoma cells against the genotoxic effects of the mycotoxin altertoxin II

Cited by 39 publications

References 36 publications

Functional impairment triggered by altertoxin II (ATXII) in intestinal cells in vitro: cross-talk between cytotoxicity and mechanotransduction

Functional impairment triggered by altertoxin II (ATXII) in intestinal cells in vitro: cross-talk between cytotoxicity and mechanotransduction

Combinatory effects of cereulide and deoxynivalenol on in vitro cell viability and inflammation of human Caco-2 cells

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

Contact Info

Product

Resources

About