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.