Archives of Toxicology

, Volume 91, Issue 12, pp 3737–3785 | Cite as

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

  • Qinghua WuEmail author
  • Xu Wang
  • Eugenie Nepovimova
  • Anca Miron
  • Qianying Liu
  • Yun Wang
  • Dongxiao Su
  • Hualin Yang
  • Li Li
  • Kamil KucaEmail author
Review Article


Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an “immune evasion” milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-κB. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.


T-2 toxin Deoxynivalenol Immunomodulation Anti-cancer Signaling pathway Autophagy Immune evasion 



Aryl hydrocarbon receptor nuclear translocator


Calcium-sensing receptor


Complement-dependent cytotoxicity


Enhancer-binding protein homologous protein


cAMP-response clement-binding protein








Fumonisin B1


Fusarenon X


Green fluorescence protein




Hemopoietic cell kinase


Hypoxia-inducible factor 1


Monoclonal antibodies


Macrophage inhibitory protein 2


Myeloid differentiation factor 88




Programmed cell death


Porcine circovirus type 2


Porcine circovirus-associated disease




RNA-activated protein kinase R


Pig polymorphonuclear cells


Peyer’s patch


Porcine reproductive and respiratory syndrome


Porcine reproductive and respiratory syndrome virus


Permeability transition pore complex


Quantitative structure activity relationship


Sheep red blood cell


Ribotoxic stress response


Structure–activity relationships


Mall molecule inhibitors


Steroid receptor coactivator




Toll-like Receptors




TNF-related apoptosis-inducing ligand


Transient receptor potential ankyrin-1


Verrucarins A



This work was supported by the National Natural Science Foundation of China (Grant No. 31602114 and 31572575), the Yangtze Fund for Youth Teams of Science and Technology Innovation (2016cqt02), the Fundamental Research Funds for the Central Universities (2662016PY115), and the project of long-term development plan UHK.

Compliance with ethical standards

Ethics statement

The manuscript does not contain clinical trials or patient data.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Qinghua Wu
    • 1
    • 2
    Email author
  • Xu Wang
    • 3
  • Eugenie Nepovimova
    • 2
  • Anca Miron
    • 4
  • Qianying Liu
    • 3
  • Yun Wang
    • 1
  • Dongxiao Su
    • 1
  • Hualin Yang
    • 1
  • Li Li
    • 1
  • Kamil Kuca
    • 2
    Email author
  1. 1.College of Life Science, Institute of BiomedicineYangtze UniversityJingzhouChina
  2. 2.Department of Chemistry, Faculty of ScienceUniversity of Hradec KraloveHradec KraloveCzech Republic
  3. 3.National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug ResiduesHuazhong Agricultural UniversityWuhanChina
  4. 4.Department of Pharmacognosy, Faculty of PharmacyUniversity of Medicine and Pharmacy Grigore T. PopaIasiRomania

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