Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential

Wu, Qinghua; Wang, Xu; Nepovimová, Eugenie; Miron, Anca; Liu, Qianying; Wang, Yun; Su, Dongxiao; Yang, Hualin; Li, Li; Kuča, Kamil

doi:10.1007/s00204-017-2118-3

Cited by 102 publications

(58 citation statements)

References 257 publications

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“…Studies in Jnk knockout mice revealed that JNK1 promotes the survival of activated T cells during immune responses and that JNK2 modulates CD8 + T cell expansion . Our group recently showed that JNK1/STAT3 is a prosurvival hub that inhibits RAW264.7 cell apoptosis . The JNK1/STAT3 pathway can maintain the normal function of mitochondria and to inhibit T‐2 toxin‐induced cell apoptosis …”

Section: The Yin and Yang Of Jnk1 And Jnk2 In The Regulation Of Cancementioning

confidence: 99%

“…68 Our group recently showed that JNK1/STAT3 is a prosurvival hub that inhibits RAW264.7 cell apoptosis. 43,69,70 The JNK1/ STAT3 pathway can maintain the normal function of mitochondria and to inhibit T-2 toxin-induced cell apoptosis. 43 JNK1 and JNK2 regulate the expression of the central transcription initiation factor TATA-binding protein (TBP).…”

Section: Fibroblastsmentioning

confidence: 99%

“…Autophagy promotes cell and organism survival in various contexts, including endoplasmic reticulum (ER) stress, ontological development, microbial infection, and diseases that are characterized by the accumulation of protein aggregates. 69,70,99 JNK positively regulates autophagy and contributes to cell survival. 46 Ogata et al 100 showed that JNK-mediated autophagy activation is essential for SK-N-SH neuroblastoma cell survival after ER stress.…”

Section: Autophagy Is Involved In Jnk-mediated Cancer Cell Survivalmentioning

confidence: 99%

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JNK signaling in cancer cell survival

et al. 2019

Medicinal Research Reviews

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146

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c‐Jun N‐terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes cancer cell survival. JNK acts synergistically with NF‐κB, JAK/STAT, and other signaling molecules to exert a survival function. JNK positively regulates autophagy to counteract apoptosis, and its effect on autophagy is related to the development of chemotherapeutic resistance. The prosurvival effect of JNK may involve an immune evasion mechanism mediated by transforming growth factor‐β, toll‐like receptors, interferon‐γ, and autophagy, as well as compensatory JNK‐dependent cell proliferation. The present review focuses on recent advances in understanding the prosurvival function of JNK and its role in tumor development and chemoresistance, including a comprehensive analysis of the molecular mechanisms underlying JNK‐mediated cancer cell survival. There is a focus on the specific “Yin and Yang” functions of JNK1 and JNK2 in the regulation of cancer cell survival. We highlight recent advances in our knowledge of the roles of JNK in cancer cell survival, which may provide insight into the distinct functions of JNK in cancer and its potential for cancer therapy.

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Section: The Yin and Yang Of Jnk1 And Jnk2 In The Regulation Of Cancementioning

confidence: 99%

Section: Fibroblastsmentioning

confidence: 99%

Section: Autophagy Is Involved In Jnk-mediated Cancer Cell Survivalmentioning

confidence: 99%

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JNK signaling in cancer cell survival

et al. 2019

Medicinal Research Reviews

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146

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“…Trichothecenes are divided into four types (A-D) depending on their characteristic functional groups [2] (Figure 1), and type A and B are greater food safety concerns because of their high toxicity and frequent occurrence in cereals, feed and food for animals and humans [2,3]. The acute uptake of trichothecenes will cause a wide variety of toxic responses in humans and animals, including gastrointestinal irritation, emesis, diarrhea, hemorrhage, leukopenia, immunosuppression and mortality [4,5].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Mitochondria: a critical target in the toxicity of trichothecenes and potential treatment strategies

Huang¹,

Cui²,

Wu³

et al. 2018

Oncotarget

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Copyright: Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTTrichothecenes are secondary metabolites produced by fungi of genus Fusarium. It was known that trichothecenes can bind to the 60S subunit of the eukaryotic ribosomes, resulting in inhibition of protein synthesis. However, emerging evidences suggest that trichothecenes can target the mitochondria to induce mitochondrial dysfunction and mitochondria-dependent apoptosis. Numerous studies have investigated the mitochondria-associated toxicities induced by trichothecenes. Here, we mainly collected the data associated with mitochondria and its relationship with trichothecene-induced toxic effects. We showed that mitochondria are the main site of reactive oxygen species production and mediate the trichothecene-induced apoptosis in various cells. The mitochondrial membrane permeabilization plays critical roles in this apoptotic process. Trichothecenes can penetrate the mitochondrial membrane due to its amphiphilic property, and inhibit the activities of mitochondrial respiratory chain complexes and electron transfer in mitochondria. Besides, trichothecenes reduce the mitochondrial biogenesis and mitochondrial transcription and translation. Peroxisome proliferator-activated receptor-γ co-activator 1α and mammalian target of rapamycin pathway are closely linked to this process. Trichothecenes can activate various microRNAs that may mediate the protein synthesis inhibition. These microRNAs may have a crosstalk with mitochondria to mediate the mitochondrial dysfunction and transcription repression in mitochondrial genome. Numerous natural compounds have been tested for their effective antioxidant and anti-inflammatorycapacities. Specially, mitochondria-targeted antioxidants and mitophagy exhibit outstanding cytoprotective abilitysince they can reduce the mitochondrial reactive oxygen species and maintain the mitochondrial quality. This review may shed some new light on the mitochondriaassociated mechanism underlying the toxicity of trichothecenes and new preventive ways to combat these mycotoxins. www.impactjournals.com/oncotarget/

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“…Interestingly, when mice were pre-treated with high dose of T-2 (4 mg/kg bw) and thereafter vaccinated with sheep red blood cells (RBCs), PA increased. But when the toxin was administered after sensitisation, significantly suppressed phagocytosis of sheep RBC was observed (Wu et al 2017).…”

Section: Immune Responsementioning

confidence: 99%

Effect of feedingBacillus cereusvar.toyoiand/or mannan oligosaccharide (MOS) on blood clinical chemistry, oxidative stress, immune response and genotoxicity in T-2 toxin exposed rabbits

Hafner

Tuboly

Mézes

et al. 2019

Italian Journal of Animal Science

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Kovács (2019) Effect of feeding Bacilluscereus var. toyoi and/or mannan oligosaccharide (MOS) on blood clinical chemistry, oxidative stress, immune response and genotoxicity in T-2 toxin exposed rabbitsa Agr ar-es K€ ornyezettudom anyi Kar, Kaposv ar University, Kaposv ar, Hungary; b J arv anytani es Mikrobiol ogiai Tansz ek, University of Veterinary Medicine, Budapest, Hungary; c Mez} ogazdas ag-es K€ ornyezettudom anyi Kar, Szent Istv an University, G€ od€ oll} o, Hungary; d MTA-KE-SZIE Mikotoxinok az Elelmiszerl ancban Kutat ocsoport, Kaposv ar, Hungary ABSTRACTThe aim of the study was to determine the effect of Bacillus cereus var. toyoi (200 mg/kg) and mannan oligosaccharide (MOS, 2 g/kg) in T-2 toxin exposed rabbits. Weaned rabbits (35 days of age) were assigned into four experimental groups (n ¼ 20 in each): control (C), B. cereus (B), MOS (M) and B. cereusþMOS (BM) group. At 49 days of age, rabbits were divided into two groups (n ¼ 10 in each), and half of the C, B, M and BM rabbits were fed with the same diet as before, but contaminated with 2 mg/kg feed T-2 toxin (groups CT, BT, MT and BMT). On day 50 and 60, rabbits were injected with ovalbumin. At 70 days of age, all animals were sacrificed. Daily weight gain was smaller in toxin challenged animals (17.6-19.5 g) compared to controls (29.7 g). Serum total protein concentration was less in toxin treated animals, among them in CT group (49.7 g/L) it decreased underneath the reference range. T-2 increased the glutathione peroxidase activity in the kidney. C and B treatments resulted in the highest IgG production. Phagocytic activity was the lowest in CT animals (76.4%), while the highest in C and BM groups (82%). Cytokine expression in the intestinal mucosa was lower in T-2 exposed animals as compared to their relevant controls. None of the feed additives had any effect on the T-2 induced changes in the oxidative stress and immune response. T-2 had slight genotoxic effect on lymphocytes, which was alleviated by MOS and B. cereus. HIGHLIGHTSThe suspected protective effect of Bacillus cereus var. toyoi and mannan oligosaccharide was investigated in T-2 toxin exposed rabbits. T-2 impaired immune response and was slightly genotoxic on lymphocytes. MOS and B. cereus alleviated the genotoxicity of T-2. ARTICLE HISTORY

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Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential

Cited by 102 publications

References 257 publications

JNK signaling in cancer cell survival

JNK signaling in cancer cell survival

WITHDRAWN: Mitochondria: a critical target in the toxicity of trichothecenes and potential treatment strategies

Effect of feedingBacillus cereusvar.toyoiand/or mannan oligosaccharide (MOS) on blood clinical chemistry, oxidative stress, immune response and genotoxicity in T-2 toxin exposed rabbits

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