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

Abstract

Evidence suggests that mistletoe extract has the potential to be used as an anticancer agent. AbnobaviscumF® is a European mistletoe extract from the host tree Fraxinus. We investigated the effect of AbnobaviscumF on the growth and survival of different leukemia cell lines. AbnobaviscumF treatment strongly reduced 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 AbnobaviscumF, we showed that AbnobaviscumF-induced cell death was associated with the activation of 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, AbnobaviscumF treatment led to both a reduction of cellular glutathione (GSH) and the induction of ER stress (GRP78 and CHOP induction and eIF-2α phosphorylation). By contrast, AbnobaviscumF did not impact the expression of the DR4 and DR5 death receptors. The AbnobaviscumF-induced apoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmk or SP600125. Our results, therefore, show that AbnobaviscumF induces apoptosis of K562 cells through the activation of the intrinsic caspase pathway, the phosphorylation of JNK-1, the reduction of cellular GSH, and the induction of ER stress.