@article{PlauthGeikowskiCichonetal.2016, author = {Plauth, Annabell and Geikowski, Anne and Cichon, Susanne and Wowro, Sylvia J. and Liedgens, Linda and Rousseau, Morten and Weidner, Christopher and Fuhr, Luise and Kliem, Magdalena and Jenkins, Gail and Lotito, Silvina and Wainwright, Linda J. and Sauer, Sascha}, title = {Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress}, series = {Free Radical Biology and Medicine}, volume = {99}, journal = {Free Radical Biology and Medicine}, doi = {10.1016/j.freeradbiomed.2016.08.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187186}, pages = {608-622}, year = {2016}, abstract = {Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general < 50 mu M), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After induction of oxidative stress by using 0.78\% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24\% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress.}, language = {en} } @article{SulimanMustafaKruegeretal.2016, author = {Suliman, Salwa and Mustafa, Kamal and Krueger, Anke and Steinm{\"u}ller-Nethl, Doris and Finne-Wistrand, Anna and Osdal, Tereza and Hamza, Amani O. and Sun, Yang and Parajuli, Himalaya and Waag, Thilo and Nickel, Joachim and Johannessen, Anne Christine and McCormack, Emmet and Costea, Daniela Elena}, title = {Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes}, series = {Biomaterials}, volume = {95}, journal = {Biomaterials}, doi = {10.1016/j.biomaterials.2016.04.002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188287}, pages = {11-21}, year = {2016}, abstract = {This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK\(^{Luc}\)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK\(^{Luc}\) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK\(^{Luc}\) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK\(^{Luc}\) both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK\(^{Luc}\) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK\(^{Luc}\), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.}, language = {en} }