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

Twardziok, M., Meierhofer, D., Börno, S. T., Timmermann, B., Jäger, S., Boral, S., et al. (2017). 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, 2017: 17:237. doi:10.1186/s12906-017-1715-2.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-CDD6-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-CDD7-1
Genre: Journal Article

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 Creators:
Twardziok, M., Author
Meierhofer, D.1, Author              
Börno, S. T.2, Author              
Timmermann, B.2, Author              
Jäger, S., Author
Boral, S., Author
Eggert, A., Author
Delebinski, C. I., Author
Seifeert, G., Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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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

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Language(s): eng - English
 Dates: 2017-04-012017-04-28
 Publication Status: Published online
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1186/s12906-017-1715-2
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Title: BMC Complementary and Alternative Medicine
Source Genre: Journal
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Publ. Info: BioMed Central
Pages: - Volume / Issue: 2017 Sequence Number: 17:237 Start / End Page: - Identifier: ISSN: 1472-6882