Enniatins are
mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible
anticancer agents. We investigated toxic effects of
enniatins A1, B and B1 isolated from Fusarium tricinctum on different
cancer cell lines. The
enniatins showed moderate activity in HepG2 and C6 cells (EC(50)-values approximately 10-25 microM), but were highly toxic in H4IIE cells (EC(50)-values approximately 1-2.5 microM). In H4IIE cells, all
enniatins increased
caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Enniatin A1, enniatin B1, and, to a lesser extent, also
enniatin B decreased the activation of extracellular regulated
protein kinase (ERK) (p44/p42), a
mitogen-activated protein kinase which is associated with cell proliferation. Furthermore,
enniatins A1 and B1, but not
enniatin B were able to inhibit moderately
tumor necrosis factor alpha (
TNF-alpha)-induced
NF-kappaB activation. Screening of 24 additional
protein kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and
metastasis) showed no inhibitory activity of
enniatins. We conclude that
enniatins A1 and B1 and, to a lesser extent,
enniatin B may possess anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Further analysis of these substances is necessary to analyse their usefulness for
cancer therapy.