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Free keywords:
Childhood cancer, Alternative medicine, Phytother
apy, ER stress, Oleanolic acid, Betulinic acid, MAPK
Abstract:
Background:
The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins
and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (
Viscum album
L.).
Commercial
Viscum album
L. extracts are aqueous, excluding the insolub
le triterpenes. We have previously shown that
mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo.
Methods:
We recreated a total mistletoe effect (viscumTT) by combining an aqueous extract (viscum) and a triterpene
extract (TT) solubilised with cyclodextrins and analysed the effects of viscumTT and the single extracts on TC-71 Ewing
sarcoma cells in vitro by transcriptomic and proteomic profiling.
Results:
Treatment with the extracts strongly impacted Ewing s
arcoma cell gene and protein expression. Apoptosis-
associated and stress-activated genes were upregulated,
proteasomal protein abundance enhanced and ribosomal and
spliceosomal proteins downregulated. The mec
hanism of action of viscum, TT and viscumTT in
TC-71 and MHH-ES-1 cells suggests the involvement of the
unfolded protein response. While viscum and viscumTT
extract treatment indicate response to oxidative stress and
activation of stress-mediated MAPK signalling, TT extract
treatment suggests the involvement of TLR signalling and autophagy.
Conclusions:
Since the combinatory extract viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma
cells in vitro, this phytopolychemotherapy could be a promisi
ng adjuvant therapeutic option for paediatric patients with
Ewing sarcoma
