title: Cefepime, a fourth-generation cephalosporin, in complex with manganese, inhibits proteasome activity and induces the apoptosis of human breast cancer cells.
abstract: Cefepime (FEP), which is a member of the fourth-generation cephalosporin class, has been extensively studied as a biochemical and antimicrobial reagent in recent years. Manganese (Mn) is important in the biochemical and physiological processes of many living organisms, and it is also high expressed in some tumor tissues. In the present study, we aimed to investigate the proteasome-inhibitory and anti-proliferative properties of 8 metal complexes (FEP‑Cu, FEP-Zn, FEP-Co, FEP-Ni, FEP-Cd, FEP-Cr, FEP-Fe, FEP-Mn) in MDA-MB‑231 human breast cancer cells. The FEP-Mn complex was found to be more potent in its ability to inhibit cell proliferation and proteasome activity than the other compounds tested. Moreover, the FEP-Mn complex inhibited proteasomal chymotrypsin-like (CT-like) activity and induced the apoptosis of breast cancer cells in a dose-and time-dependent manner. Furthermore, the MCF-10A cells were much less sensitive to the FEP complexes compared with the MDA-MB-231 breast cancer cells. These results demonstrated that the FEP-Mn(II) complex has the potential to act as a proteasome inhibitor and apoptosis inducer and therefore has possible future applications in cancer chemotherapy.
authors.affiliation: School of Pharmacy, Jining Medical University, Rizhao, Shandong 276826, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, Shandong 266100, P.R. China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Bi
authors.affiliation: Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, Shandong 266100, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining, Shandong 272100, P.R. China.
authors.forename: Huannan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, Shandong 266100, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000077723:Cefepime; D045744:Cell Line, Tumor; D002511:Cephalosporins / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: D002511:Cephalosporins; D009363:Neoplasm Proteins; D061988:Proteasome Inhibitors; D003300:Copper; D000077723:Cefepime; D046988:Proteasome Endopeptidase Complex