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The Newly Synthetized Chalcone L1 Is Involved in the Cell Growth Inhibition,Induction of Apoptosis and Suppression of Epithelial-to-Mesenchymal Transition of HeLa Cells
Authors:Tomas Kuruc  Martin Kello  Klaudia Petrova  Zuzana Kudlickova  Peter Kubatka  Jan Mojzis
Institution:1.Department of Pharmacology, Faculty of Medicine, P. J. Safarik University, 04011 Košice, Slovakia; (T.K.); (K.P.);2.Department of Chemistry, Biochemistry and Biophysics, University of Veterinary Medicine and Pharmacy, 04181 Košice, Slovakia;3.Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
Abstract:Over the past decades, natural products have emerged as promising agents with multiple biological activities. Many studies suggest the antioxidant, antiangiogenic, antiproliferative and anticancer effects of chalcones and their derivatives. Based on these findings, we decided to evaluate the effects of the newly synthetized chalcone L1 in a human cervical carcinoma cell (HeLa) model. Presented results were obtained by western blot and flow cytometric analyses, live cell imaging and antimigratory potential of L1 in HeLa cells was demonstrated by scratch assay. In the present study, we proved the role of L1 as an effective agent with antiproliferative activity supported by G2/M cell cycle arrest and apoptosis. Moreover, we proved that L1 is involved in modulating Transforming Growth Factor-β1 (TGF-β) signal transduction through Smad proteins and it also modulates other signalling pathways including Akt, JNK, p38 MAPK, and Erk1/2. The involvement of L1 in epithelial-to-mesenchymal transition was demonstrated by the regulation of N-cadherin, E-cadherin, and MMP-9 levels. Here, we also evaluated the effect of conditioned medium from BJ-5ta human foreskin fibroblasts in HeLa cell cultures with subsequent L1 treatment. Taken together, these data suggest the potential role of newly synthesized chalcone L1 as an anticancer-tumour microenvironment modulating agent.
Keywords:chalcones  antiproliferative  apoptosis  TGF-β    conditioned medium  epithelial-to-mesenchymal transition  tumour microenvironment  migration  HeLa cells
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