Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe extract
- Author(s)
- YU-KYOUNG PARK; YOUNG ROK DO; BYEONG-CHURL JANG
- Keimyung Author(s)
- Jang, Byeong Churl; Do, Young Rok
- Department
- Dept. of Molecular Medicine (분자의학)
Dept. of Internal Medicine (내과학)
- Journal Title
- Oncology Reports
- Issued Date
- 2012
- Volume
- 28
- Issue
- 6
- Keyword
- Abnobaviscum F®; caspase-9; JNK-1; myeloid cell leukemia-1; glutathione; ER stress; K562
- Abstract
- Evidence suggests that mistletoe extract has the potential to be used as an anticancer agent. Abnobaviscum F® is a European mistletoe extract from the host tree Fraxinus. We investigated the effect of Abnobaviscum F on the growth and survival of different leukemia cell lines. Abnobaviscum F 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 Abnobaviscum F, we showed that Abnobaviscum F-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, Abnobaviscum F 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, Abnobaviscum F did not impact the expression of the DR4 and DR5 death receptors. The Abnobaviscum F-induced apoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmk or SP600125. Our results, therefore, show that Abnobaviscum F 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.
Key words: Abnobaviscum F®, caspase-9, JNK-1, myeloid cell leukemia-1, glutathione, ER stress, K562
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