Genistein and delphinidin antagonize the genotoxic effects of the mycotoxin alternariol in human colon carcinoma cells

Aichinger, Georg; Beisl, Julia; Marko, Doris

doi:10.1002/mnfr.201600462

Cited by 38 publications

(33 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternaria alternata proliferates on food items and can contaminate commodities which may also reach the market (Walravens et al 2016). Alternaria mycotoxins can differ greatly in structure and their biological targets span from the regulation of DNA topology to the estrogenic cascade (Aichinger et al 2017; Jarolim et al 2016; Lehmann et al 2006; Vejdovszky et al 2017a). Among these, the perylene quinone type mycotoxin altertoxin II (ATXII) is one of the more potent ones with respect to genotoxicity (Fleck et al 2016; Pahlke et al 2016; Schwarz et al 2012).…”

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

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: 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

“…[12][13][14] Polyphenols provide a wide range of anti-carcinogenic health benefits. [15][16][17][18][19][20][21][22] However, polyphenol absorption is reportedly very low.…”

Section: Introductionmentioning

confidence: 99%

Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells

Zhao

Shi

Guo

et al. 2017

Molecular Carcinogenesis

View full text Add to dashboard Cite

Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose‐dependently decreased cell proliferation, delayed cell migration, and decreased matrix metalloproteinas‐9 (MMP‐9) activity. In addition, inhibition of autophagy by Atg5‐siRNA, caspases by Z‐VAD‐FMK suppressed urolithin A‐stimulated cell death and anti‐metastatic effects. Micromolar urolithin A concentrations induced both autophagy and apoptosis. Urolithin A suppressed cell cycle progression and inhibited DNA synthesis. These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human CRC cell metastasis. Urolithins may thus contribute to CRC treatment and offer an alternative or adjunct chemotherapeutic agent to combat this disease.

show abstract

“…γ‐H2AX formation is a rapid and sensitive cellular response to the presence of DSBs (Celeste et al, ; Ibuki & Toyooka, ). Previous studies had shown that 100 μM GES could induce significant genotoxicity in other cell systems (Aichinger, Beisl, & Marko, ); so here we exposed 100 μM GES for 1, 3, 6 and 9 hr to dynamically determine the number of γ‐H2AX foci in the WT TK6 cells. As shown in Figure a,b the numbers of γ‐H2AX foci were significantly increased after treatment of 100 μM GES, and peaked at 6 hr.…”

Section: Resultsmentioning

confidence: 99%

Genistein‐induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells

Líu

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Genistein (GES), a phytoestrogen, has potential chemopreventive and chemotherapeutic effects on cancer. The anticancer mechanism of GES may be related with topoisomerase II associated DNA double-strand breaks (DSBs). However, the precise molecular mechanism remains elusive. Here, we performed genetic analyses using human lymphoblastoid TK6 cell lines to investigate whether non-homologous DNA end joining (NHEJ) and homologous recombination (HR), the two major repair pathways of DSBs, were involved in repairing GES-induced DNA damage. Our results showed that GES induced DSBs in TK6 cells. Cells lacking Ligase4, an NHEJ enzyme, are hypersensitive to GES. Furthermore, the sensitivity of Ligase4 cells was associated with enhanced DNA damage when comparing the accumulation of γ-H2AX foci and number of chromosomal aberrations (CAs) with WT cells. In addition, cells lacking Rad54, a HR enzyme, also presented hypersensitivity and increased DNA damages in response to GES. Meanwhile, Treatment of GES-lacking enhanced the accumulation of Rad51, an HR factor, in TK6 cells, especially in Ligase4 . These results provided direct evidence that GES induced DSBs in TK6 cells and clarified that both NHEJ and HR were involved in the repair of GES-induced DNA damage, suggesting that GES in combination with inhibition of NHEJ or HR would provide a potential anticancer strategy.

show abstract

Genistein and delphinidin antagonize the genotoxic effects of the mycotoxin alternariol in human colon carcinoma cells

Abstract: Our data indicate that a respective polyphenol-rich diet might aid to protect against genotoxic damages caused by AOH, whereby bioactive concentrations of DEL are predominantly expected locally in the intestines.

Cited by 38 publications

References 41 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

Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells

Genistein‐induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells

Contact Info

Product

Resources

About