ABSTRACT
Cisplatin remains the most widely used chemotherapeutic agent in cancer treatment; however, its inherent drawbacks have fueled the development of novel metalloanticancer drugs. In this study, two novel Cu(II) complexes (Cu1 and Cu2) were designed and synthesized. Notably, these Cu(II) complexes showed higher cytotoxicity against HL-7402 cells than cisplatin. Moreover, Cu(II) complexes significantly inhibited liver cancer growth in a xenograft model. A mechanism study revealed that the Cu(II) complexes reduced the mitochondrial membrane potential of cancer cells, produced excessive reactive oxygen species (ROS), induced mitochondrial DNA (mtDNA) damage, and ultimately facilitated cancer cell apoptosis.
Subject(s)
Antineoplastic Agents , Apoptosis , Coordination Complexes , Copper , DNA Damage , DNA, Mitochondrial , Liver Neoplasms , Mitochondria , Reactive Oxygen Species , Humans , Copper/chemistry , Copper/pharmacology , Apoptosis/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Animals , DNA Damage/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice , Mitochondria/drug effects , Mitochondria/metabolism , DNA, Mitochondrial/metabolism , DNA, Mitochondrial/genetics , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effects , Cell Line, Tumor , Hydrazones/pharmacology , Hydrazones/chemistry , Hydrazones/chemical synthesis , Xenograft Model Antitumor Assays , Mice, Nude , Mice, Inbred BALB CABSTRACT
OBJECTIVES: Pre-eclampsia (PE) affects many women worldwide and remains the leading cause of morbidity and mortality in neonatal and maternal settings. Abnormal expression of placental microRNAs (miRNAs) may be associated with PE. MATERIAL AND METHODS: This study was conducted to the relationship between IGF1 and the expression spectrum of miRNA in the placenta of preeclampsia patient. The expression of miRNA in placental tissue was compared between pre-eclampsia (n = 6) and normal pregnant women (n = 5) miRNA targets were studied by computer simulation and functional assays. The role of miRNA was verified in trophoblast cell lines by apoptosis assay and invasion assay. RESULTS: There was a significant increase in miRNAs in the placenta of women with pre-eclampsia compared with patients with normal pregnancy. Luciferase assay confirmed direct regulation of miRNA. CONCLUSIONS: The expression of IGF1 and miRNA was significantly increased in the placenta of patients with pre-eclampsia.