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Extracts  of mistletoe (Viscum album) are intensively used in complementary  medicine, but their mechanisms are not fully understood in most cases, and the  effects on metabolism have not been investigated in detail. However, some  biologically active natural products are well known to provoke unexpected  cellular responses. They reduce overexpression of heat shock proteins (Hsps) in  cancer cells. The aim of the current study was to determine whether methanolic  extract of V. album, which possesses antioxidant activity, has an effect  on expression levels of Hsp27 and 14-3-3 proteins in a C6 glioma cell line. For  the first time, the apoptosis-inducing effect of this extract was also  determined via caspase-3 activation in the cells. Overexpression of Hsps was  induced by heat shock at 42°C for 1 h. Expression levels of Hsp27 and 14-3-3  proteins were determined using Western blot analysis. The apoptosis-inducing  effect was also evaluated via caspase-3 activation in C6 glioma cells.  Pretreatment of the cells with a nontoxic dose (100 μg/mL) of V.  album extract before heat shock significantly reduced expression levels of  Hsp27 (73%) and 14-3-3β (124%), 14-3-3γ (23%), and 14-3-3ζ (84%) proteins.  Pretreatment with the extract before heat shock increased apoptosis via  caspase-3 activation (60%) in C6 glioma cells. This result suggested that the  methanolic extract of V. album downregulates expression of Hsp27 and 14-3-3  chaperone proteins and induces apoptosis, which warrants further exploration as  a potential bioactive compound for cancer therapy.

Extract from mistletoe, Viscum album L., reduces Hsp27 and 14-3-3 protein expression and induces apoptosis in C6 rat glioma cells