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

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 insoluble 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 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. Conclusions Since 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

New insight into kinetics behavor of the structural formation process in Agar gelation

A time-resolved experimental study on the kinetics and relaxation of the structural formation process in gelling Agar-water solutions was carried out using our custom-built torsion resonator. The study was based on measurements of three naturally cooled solutions with agar concentrations of 0.75%, 1.0% and 2.0% w/w. It was found that the natural-cooling agar gelation process could be divided into three stages, sol stage (Stage I), gelation zone (Stage II) and gel stage (Stage III), based on the time/temperature evolutions of the structural development rate (SDR). An interesting fluctuant decaying behavior of SDR was observed in Stage II and III, indicative of a sum of multiple relaxation processes and well described by a multiple-order Gaussisn-like equation: . More interestingly, the temperature dependences of the fitted values of Wn in Stage II and Stage III were found to follow the different Arrhenius laws, with different activation energies of EaII= 39-74 KJ/mol and EaIII~7.0 KJ/mol. The two different Arrhenius-like behaviors respectively suggest that dispersions in Stage II be attributed to the relaxation of the self-assembly of agar molecules or the growth of junction zones en route to gelation, in which the formation or fission of hydrogen bonding interactions plays an important role; and that dispersions in Stage III be attributed to the relaxation dynamics of water released from various size domains close to the domain of the viscous flow of water during the syneresis process.Comment: 24 pages, 4 figures, 1 tabl