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Evidence suggests that mistletoe extract has the potential to be used asan anticancer agent. Abnobaviscum F® is a European mistletoe extract from thehost tree Fraxinus. We investigated the effect of Abnobaviscum F on the growthand survival of different leukemia cell lines. Abnobaviscum F treatment stronglyreduced survival and induced apoptosis of K562 (human myeloid leukemia), RPMI-8226(human plasmacytoma) and L1210 (murine lymphocytic leukemia) cells in culture.Using K562 cells to further investigate the mechanism of action of Abnobaviscum F,we showed that Abnobaviscum F-induced cell death was associated with the activationof caspase-9, JNK-1/2 and p38 MAPK, as well as with the downregulation of Mcl-1,and inhibition of ERK-1/2 and PKB phosphorylation. Moreover, Abnobaviscum F treatmentled to both a reduction of cellular glutathione (GSH) and the induction of ERstress (GRP78 and CHOP induction and eIF-2α phosphorylation). By contrast, Abnobaviscum Fdid not impact the expression of the DR4 and DR5 death receptors. The Abnobaviscum F-inducedapoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmkor SP600125. Our results, therefore, show that Abnobaviscum F induces apoptosisof K562 cells through the activation of the intrinsic caspase pathway, the phosphorylationof JNK-1, the reduction of cellular GSH, and the induction of ER stress.

Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe extract