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- ItemIn vitro studies of polyhedral oligo silsesquioxanes: Evidence for their low cytotoxicity(Basel : MDPI, 2015) Janaszewska, Anna; Gradzinska, Kinga; Marcinkowska, Monika; Klajnert-Maculewicz, Barbara; Stanczyk, Wlodzimierz A.As scientific literature considers polyhedral oligosilsesquioxanes (POSS) as potential drug delivery systems, it is necessary to check their impact on mammalian cells. Toxicity of octaammonium chloride salt of octaaminopropyl polyhedral oligomeric silsesquioxane (oap-POSS) towards two cell lines: mouse neuroblastoma (N2a) and embryonic mouse hippocampal cells (mHippoE-18) was studied. Experiments consisted of analysis of a cell cycle, cell viability, amount of apoptotic and necrotic cells, and generation of reactive oxygen species (ROS). POSS caused a shift in the cell population from the S and M/G2 phases to the G0/G1 phase. However, the changes affected less than 10% of the cell population and were not accompanied by increased cytotoxicity. POSS did not induce either apoptosis or necrosis and did not generate reactive oxygen species. A cytotoxicity profile of POSS makes it a promising starting material as drug carrier.
- ItemThe novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells(London : BioMed Central, 2014) Kretzschmar, C.; Roolf, C.; Langhammer, T.-S.; Sekora, A.; Pews-Davtyan, A.; Beller, M.; Frech, M.J.; Eisenlöffel, C.; Rolfs, A.; Junghanss, C.Background: Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3β inhibitor, on several ALL cell lines.Methods: ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points.Results: PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 μM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase.Conclusion: PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL.