Anticancer Activity of the Fusarium Toxin Enniatin

1
Anticancer Activity of the Fusarium Toxin Enniatin
R. Dornetshubera, P. Heffeterb, L. Elblingb, M.
Mickscheb, W. Bergerb, R. Lemmens-Grubera aInstitu
te of Pharmacology and Toxikology, University of
Vienna bInstitute of Cancer Research, Medical
University of Vienna
 Enniatin, a cyclic hexadepsipeptide, is a
secondary metabolite, produced by various strains
of the genus Fusarium. It is reported to have
antibiotic, insecticidal and ionophoric activity.
In this study we investigated whether enniatin
also has anticancer activity. For this purpose we
used several human cancer cell models. The IC50
of enniatin against all tested cell lines was in
low µM range. Moreover, ABC-transporter
overexpression (PGP, MRP1 and BCRP) had no
influence on the anticancer activity of
enniatin. Cell shrinkage, chromatin condensation,
and apoptotic bodies, all indicating apoptosis,
were shown after 24 hrs treatment with 5µM and
10µM enniatin by DAPI staining. Correspondingly,
PARP cleavage was detectable in Western blot
analysis. This was accompanied by the loss of
mitochondrial membrane potential (JC-1 staining).
Additionally no signs of necrosis like release of
lactate dehydrogenase (LDH) were detectable after
treatment with enniatin for 24 hrs. To monitor
effects of enniatin on the cell cycle
progression, the incorporation of the radioactive
3H-thymidine into DNA was measured. Enniatin
treatment led to cell cycle arrest which was
further characterized as occuring in G2-M phase
(probidium iodide staining, FACS analysis). In
summary, the Fusarium toxin enniatin has
anticancer activity in vitro, which is not
influenced by ABC-transporter overexpression. The
cytotoxic activity of this natural drug is based
on the induction of apoptosis and an arrest in
G2-M phase. Although further experiments with
this substance have to be conducted the results
up to now show promise for enniatin in cancer
therapy.
Apoptotic cell death
Conclusion

• Enniatin shows anticancer activity which is not
  reduced by ABC transporter overexpression.
• ? Exposure to Enniatin leads to loss of
  mitochondrial membrane potential and accordingly
  to apoptosis.
• Cells exposed to Enniatin are arrested at low
  concentrations in S- and higher in G2-M phase.