title: ROS-mediated autophagy was involved in cancer cell death induced by novel copper(II) complex.
abstract: In this study, we investigated autophagy induced in HeLa cells by copper(II) complex of ethyl 2-[bis(2-pyridylmethyl)amino] propionate ligand (ETDPA) (formula: [(ETDPA)Cu(phen)](ClO4)2 (abbreviated as LCu),a novel synthetic copper(II) complex whose DNA binding activity has been proved. Cell viability, autophagic levels and generation of ROS were evaluated following the exposure to LCu. LCu-induced cell death in a dose- and time-dependent manner, which was demonstrated by enhanced fluorescence intensity of monodansylcadervarine (MDC), as well as elevated expression of autophagy-related protein MAP-LC3. These phenomena were all attenuated after pretreatment with autophagy inhibitors 3-MA or NH(4)Cl. Furthermore, our data indicated that LCu-triggered autophagy through ROS: cellular ROS levels were increased after LCu treatment, which was reversed by ROS scavenger NAC (N-acetylcysteine). As a consequence, Lcu-mediated autophagy was partly blocked by NAC. In summary, we synthesized a novel copper(II) complex and showed that this compound was effective in killing HeLa cells via ROS-triggered autophagic pathway.
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Guo
authors.forename: Si-si
authors.initials: SS
authors.lastname: Ye
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Qiu-yun
authors.initials: QY
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C523706:(Cu(4-methylcoumarin-6,7-dioxactetate)(phenanthroline)2); D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species