title: Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway.
abstract: Silver complexes have been shown to possess antimicrobial and anticancer properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, was synthesized in our previous study. In this study, we offer evidence that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis was associated with the levels of intracellular ROS. The further study revealed that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the caspase-3 activation and led to the translocation of apoptosis inducing factor and endonucleaseG to the nucleus. These findings have important implications for the development of silver complexes for anticancer applications.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Senpeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Shandong University Qilu Hospital, Jinan, Shandong 250012, PR China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan 250353, PR China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Tan
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan 250353, PR China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, PR China. Electronic address: zhaoyunxue@sdu.edu.cn.
authors.forename: Yunxue
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002193:Cantharidin / Q000031:analogs & derivatives* / Q000737:chemistry*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011522:Protons; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012834:Silver / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011108:Polymers; D011522:Protons; D017382:Reactive Oxygen Species; D012834:Silver; D002193:Cantharidin
keywords: Ag-SP-DNC; Apoptosis; Lung cancer; Mitochondria; Reactive oxygen species