caa a22 4500 445313269 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0347-8 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0347-8 New 4-Maleamic Acid and 4-Maleamide Peptidyl Chalcones as Potential Multitarget Drugs for Human Prostate Cancer [Elektronische Daten] [Juan Rodrigues, Claudia Abramjuk, Luis Vásquez, Neira Gamboa, José Domínguez, Bianca Nitzsche, Michael Höpfner, Radostina Georgieva, Hans Bäumler, Carsten Stephan, Klaus Jung, Michael Lein, Anja Rabien] ABSTRACT: Purpose: The objective of this study was to investigate the effect of new 4-maleamic acid and 4-maleamide peptidyl chalcone derivatives against human prostate cancer in vitro and in vivo. Methods: From a series of 21 chalcones, the effects of the three best inhibitors of PC-3 and LNCaP cell viability on growth, including cell cycle changes, adhesion, migration, and cell invasion, as well as their ability to inhibit angiogenesis, clonogenic activity, and matrix metalloproteinases MMP-2 and MMP-9, were tested. The effects in vivo were studied in PC-3 and LNCaP xenografts. Results: Three of the examined chalcones reduced cell viability in both cell lines in a strong dose- and time-dependent manner. An inhibition of the cell cycle progress was observed. These changes were accompanied with the inhibition of cell adhesion, migration, and invasion as well as with reduced neovascularization in chick embryos, tumor colony formation, and MMP-9 activity. The in vivo results demonstrated the strong activity of these structures as inhibitors of tumor development in nude mice compared to non-treated animals. Conclusion: The results suggest the multitarget efficacy of 4-maleamic acid and 4-maleamide peptidyl chalcones against human prostate cancer cells and emphasize the potential therapeutic relevance of these compounds. Springer Science+Business Media, LLC, 2010 angiogenesis nationallicence chalcones nationallicence LNCaP and PC-3 xenografts nationallicence matrix metalloproteinase-9 nationallicence prostate cancer nationallicence CAM : chick chorioallantoic membrane nationallicence CI : cell index nationallicence DMSO : dimethyl sulfoxide nationallicence ECM : extracellular matrix nationallicence IC50 : concentration required for 50% inhibition of the tumor cell viability nationallicence LNCaP : human prostate cancer cell line, hormone-dependent nationallicence MMP : matrix metalloproteinase nationallicence PBS : phosphate-buffered saline nationallicence PC-3 : human prostate cancer cell line, hormone-independent nationallicence PCa : prostate cancer nationallicence PI : propidium iodide nationallicence Rodrigues Juan Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Abramjuk Claudia Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Vásquez Luis Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut Gamboa Neira Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut Domínguez José Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut Nitzsche Bianca Department of Physiology, University Hospital Charité, Berlin, Germany aut Höpfner Michael Department of Physiology, University Hospital Charité, Berlin, Germany aut Georgieva Radostina Institute of Transfusion Medicine, University Hospital Charité, Berlin, Germany aut Bäumler Hans Institute of Transfusion Medicine, University Hospital Charité, Berlin, Germany aut Stephan Carsten Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Jung Klaus Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Lein Michael Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Rabien Anja Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 907-919 0724-8741 28:4<907 2011 28 11095 https://doi.org/10.1007/s11095-010-0347-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0347-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rodrigues Juan Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 700 1- Abramjuk Claudia Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 700 1- Vásquez Luis Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut NATIONALLICENCE 700 1- Gamboa Neira Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut NATIONALLICENCE 700 1- Domínguez José Laboratory of Biochemistry and Laboratory of Organic Synthesis School of Pharmacy, Central University of Venezuela, Caracas, Venezuela aut NATIONALLICENCE 700 1- Nitzsche Bianca Department of Physiology, University Hospital Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Höpfner Michael Department of Physiology, University Hospital Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Georgieva Radostina Institute of Transfusion Medicine, University Hospital Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Bäumler Hans Institute of Transfusion Medicine, University Hospital Charité, Berlin, Germany aut NATIONALLICENCE 700 1- Stephan Carsten Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 700 1- Jung Klaus Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 700 1- Lein Michael Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 700 1- Rabien Anja Department of Urology, University Hospital Charité, Schumannstrasse 20/21, 10117, Berlin, Germany aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 907-919 0724-8741 28:4<907 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer