l -Ornithine Schiff base-copper and -cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells

Verfasser / Beitragende:
[Zhongyu Zhang, Caifeng Bi, Yuhua Fan, Nan Zhang, Rahul Deshmukh, Xingchen Yan, Xiuwen Lv, Pengfei Zhang, Xia Zhang, Q. Dou]
Ort, Verlag, Jahr:
2015
Enthalten in:
JBIC Journal of Biological Inorganic Chemistry, 20/1(2015-01-01), 109-121
Format:
Artikel (online)
ID: 605506949
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024 7 0 |a 10.1007/s00775-014-1219-1  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00775-014-1219-1 
245 0 0 |a l -Ornithine Schiff base-copper and -cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells  |h [Elektronische Daten]  |c [Zhongyu Zhang, Caifeng Bi, Yuhua Fan, Nan Zhang, Rahul Deshmukh, Xingchen Yan, Xiuwen Lv, Pengfei Zhang, Xia Zhang, Q. Dou] 
520 3 |a Ubiquitin-proteasome system (UPS) plays a crucial role in many cellular processes such as cell cycle, proliferation and apoptosis. Aberrant activation of UPS may result in cellular transformation or other altered pathological conditions. Previous studies have shown that metal-based complexes could inhibit proteasome activity and induce apoptosis in certain human cancer cells. In the current study, we report that the cadmium and copper complexes with heterocycle-ornithine Schiff base are potent inhibitors of proteasomal chymotrypsin-like (CT-like) activity, leading to induction of apoptosis in cancer cells. Two novel copper-containing complexes and two novel cadmium-containing complexes with different heterocycle-ornithine Schiff base structures as ligands were synthesized and characterized. We found that complexes Cu1, Cd1 and Cd2 show proteasome-inhibitory activities in human breast cancer MDA-MB-231 and human prostate cancer LNCaP cells, resulting in the accumulation of p27, a natural proteasome substrate and other ubiquitinated proteins, followed by the induction of apoptosis. Our results suggest that metal complexes with heterocycle-ornithine Schiff base have proteasome-inhibitory capabilities and have the potential to be developed into novel anticancer drugs. Graphical Abstract: 
540 |a SBIC, 2014 
690 7 |a Proteasome inhibitors  |2 nationallicence 
690 7 |a Apoptosis  |2 nationallicence 
690 7 |a Copper  |2 nationallicence 
690 7 |a Cadmium  |2 nationallicence 
690 7 |a Metal-based anticancer drugs  |2 nationallicence 
690 7 |a DMSO : Dimethyl sulfoxide  |2 nationallicence 
690 7 |a MTT : 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide  |2 nationallicence 
690 7 |a PARP : Poly(ADP-ribose) polymerase  |2 nationallicence 
690 7 |a PBS : Phosphate-buffered saline  |2 nationallicence 
690 7 |a Suc-LLVY-AMC : N-Succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin  |2 nationallicence 
690 7 |a UPS : Ubiquitin-proteasome system  |2 nationallicence 
700 1 |a Zhang  |D Zhongyu  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Bi  |D Caifeng  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Fan  |D Yuhua  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Zhang  |D Nan  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Deshmukh  |D Rahul  |u Department of Oncology, Pharmacology and Pathology, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, 48201, Detroit, MI, USA  |4 aut 
700 1 |a Yan  |D Xingchen  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Lv  |D Xiuwen  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Zhang  |D Pengfei  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Zhang  |D Xia  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
700 1 |a Dou  |D Q.  |u Department of Oncology, Pharmacology and Pathology, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, 48201, Detroit, MI, USA  |4 aut 
773 0 |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/1(2015-01-01), 109-121  |x 0949-8257  |q 20:1<109  |1 2015  |2 20  |o 775 
856 4 0 |u https://doi.org/10.1007/s00775-014-1219-1  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00775-014-1219-1  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Zhongyu  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bi  |D Caifeng  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fan  |D Yuhua  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Nan  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Deshmukh  |D Rahul  |u Department of Oncology, Pharmacology and Pathology, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, 48201, Detroit, MI, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yan  |D Xingchen  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lv  |D Xiuwen  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Pengfei  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Xia  |u Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, 238 Songling Road, 266100, Qingdao, Shandong, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Dou  |D Q.  |u Department of Oncology, Pharmacology and Pathology, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, 540.1 HWCRC, 4100 John R Road, 48201, Detroit, MI, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/1(2015-01-01), 109-121  |x 0949-8257  |q 20:1<109  |1 2015  |2 20  |o 775