We
screened thirty-four methanolic plant extracts for inhibition of constitutive nuclear factor κB (NF- κB)
activity by a NF- κB-luciferase reporter gene assay. Strong inhibition of NF- κB activity was found in extracts of leaf and rhizome
from Nuphar lutea L. SM. (Nuphar). Dimeric
sesquiterpene thioalkaloids were found to be the major components of the
partially purified extract. The nuphar alkaloids mixture (NUP) showed a dose
dependent inhibition of NF-κB activity in a luciferase reporter gene assay as
well as reduction of nuclear NF-κB subunits expression as tested by western
blots and immuno-histochemistry. Decreased DNA binding was demonstrated in
Electro Mobility Shift Assays (EMSA). NUP inhibited both inducible and
constitutive NF-κB activation and affected the canonical and alternative
pathways. Suppression of NF- κB was not cell type specific.
Induction of apoptosis by the alkaloid mixture was demonstrated by
time-dependent and dose-dependent cleavage of procaspase-9 and PARP.
Synergistic cytotoxicity of the active mixture with cisplatin and etoposide was
demonstrated (1). In addition, in vivo experiments demonstrated
that NUP partially protected mice from LPS- induced septic shock and from experimental
B16 melanoma lung metastasis. Overall, our results show that NUP inhibits the
NF-κB pathway and acts as a sensitizer to conventional chemotherapy, enabling
the search for its specific target and its application against cancer and
inflammation.
(1) Ozer et al. Cancer Biology & Therapy. 8:1860-1868; 2009. Commented in
Efferth T. Cancer Biology & Therapy 8:1869-1870; 2009
