The secondary Fusarium metabolite aurofusarin induces oxidative stress, cytotoxicity and genotoxicity in human colon cells

Jarolim, Katharina; Wolters, Konstantin; Woelflingseder, Lydia; Pahlke, Gudrun; Beisl, Julia; Puntscher, Hannes; Braun, Dominik; Sulyok, Michael; Warth, Benedikt; Marko, Doris

doi:10.1016/j.toxlet.2017.12.008

Cited by 30 publications

(30 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We therefore used the low level of 1 µM to limit cytotoxicity and to be able to observe possible combinatory effects with the trichothecenes. Despite its reported pro-oxidative properties [25], AURO modulated NF-κB activity only marginally (Figure 2A). At 5 and 10 µM significant cytotoxic effects were detected, concomitantly with a decrease in NF-κB activity.…”

Section: Discussionmentioning

confidence: 88%

“…Low or transient levels of ROS are reported to trigger an inflammatory response through activation of the NF-κB signaling pathway [51][52][53]. Recently, the dimeric naphthoquinone AURO was shown to enhance intracellular ROS levels causing significant pro-oxidative DNA damage in HT-29 cells [25]. High levels of AURO contamination were reported in occurrence studies analyzing various food and feed components [4,5,29].…”

Section: Discussionmentioning

confidence: 99%

“…However, the impact of AURO on the NF-κB signaling pathway and potential combinatory interactions with co-occurring trichothecenes such as DON and NX-3 on the inflammatory response have not been addressed yet. AURO is known to be rather unstable and concentrations of about 10 µM were already reported to induce pronounced cytotoxic effects in the used cell systems [25,54]. We therefore used the low level of 1 µM to limit cytotoxicity and to be able to observe possible combinatory effects with the trichothecenes.…”

Section: Discussionmentioning

confidence: 99%

“…Among many other aspects, oxidative stress plays an essential role in the pathogenesis and progression of IBDs [24]. Another Fusarium secondary metabolite reported to induce oxidative stress in human colon adenocarcinoma cells HT-29, is the coloring pigment aurofusarin (AURO, Figure 1C) [25]. Even though AURO was already isolated in 1937 from the mycelium of Fusarium culmorum [26], toxicological studies are still limited.…”

Section: Introductionmentioning

confidence: 99%

“…Even though AURO was already isolated in 1937 from the mycelium of Fusarium culmorum [26], toxicological studies are still limited. In HT-29 and HCEC-1CT cells, Jarolim, Wolters, Woelflingseder, Pahlke, Beisl, Puntscher, Braun, Sulyok, Warth and Marko [25] reported AURO to be cytotoxic at concentrations ≥ 1 µM. Although AURO is frequently found at high concentrations in various food commodities [27][28][29], immunomodulatory effects have not been assessed yet.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Pro-Inflammatory Effects of NX-3 Toxin Are Comparable to Deoxynivalenol and not Modulated by the Co-Occurring Pro-Oxidant Aurofusarin

et al. 2020

Self Cite

View full text Add to dashboard Cite

The type A trichothecene NX-3, produced by certain Fusarium graminearum strains, is similar to the mycotoxin deoxynivalenol (DON), with the exception that it lacks the carbonyl moiety at the C-8 position. NX-3 inhibits protein biosynthesis and induces cytotoxicity to a similar extent as DON, but so far, immunomodulatory effects have not been assessed. In the present study, we investigated the impact of NX-3 on the activity of the nuclear factor kappa B (NF-κB) signaling pathway in direct comparison to DON. Under pro-inflammatory conditions (IL-1β treatment), the impact on cytokine mRNA levels of NF-κB downstream genes was studied in human colon cell lines, comparing noncancer (HCEC-1CT) and cancer cells (HT-29). In addition, potential combinatory effects with the co-occurring Fusarium secondary metabolite aurofusarin (AURO), a dimeric naphthoquinone known to induce oxidative stress, were investigated. NX-3 and DON (1 μM, 20 h) significantly activated a NF-κB regulated reporter gene to a similar extent. Both trichothecenes also enhanced transcript levels of the known NF-κB-dependent pro-inflammatory cytokines IL-8, IL-6, TNF-α and IL-1β. Comparing the colon cancer HT-29 and noncancer HCEC-1CT cells, significant differences in cytokine signaling were identified. In contrast, AURO did not affect NF-κB pathway activity and respective cytokine expression levels at the tested concentration. Despite its pro-oxidant potency, the combination with AURO did not significantly affect the immunomodulatory effects of the tested trichothecenes. Taken together, the present study reveals comparable potency of DON and NX-3 with respect to immunomodulatory and pro-inflammatory potential. Consequently, not only DON but also NX-3 should be considered as factors contributing to intestinal inflammatory processes.

show abstract

Section: Discussionmentioning

confidence: 88%