Transcriptomic and proteomic insight into the effects of a defined European mistletoe extract in Ewing sarcoma cells reveals cellular stress responses

BMC Complementary and Alternative Medicine

Research Article

S. Jäger¹  G. Seifert²  C. I. Delebinski²  A. Eggert²  M. Twardziok³  Sengül Boral⁴  D. Meierhofer⁵  S. Börno⁵  B. Timmermann⁵ 

[1] Birken AG, Niefern-Oeschelbronn, Germany;Department of Paediatric Oncology/Hematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Paediatric Oncology/Hematology, Otto Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany;Institute of Pharmacy, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany;Department of Paediatrics, Dr. von Haunersches Kinderspital, Klinikum der Universität München, Munich, Germany;Department of Pathology, Charité, Universitätsmedizin Berlin, Berlin, Germany;Max Planck Institute for Molecular Genetics, Berlin, Germany;

关键词: Childhood cancer;    Alternative medicine;    Phytotherapy;    ER stress;    Oleanolic acid;    Betulinic acid;    MAPK;   

DOI  :  10.1186/s12906-017-1715-2

 received in 2016-08-31, accepted in 2017-04-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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 insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo.MethodsWe 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.ResultsTreatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism 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.ConclusionsSince the combinatory extract viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.

【 授权许可】

CC BY   
© The Author(s). 2017