title: A ROS-mediated lysosomal-mitochondrial pathway is induced by a novel Amonafide analogue, 7c, in human Hela cervix carcinoma cells.
abstract: In this study, a novel naphthalimide derivative 7c was designed which is topo II inhibiting though owning weak DNA binders. It was shown that 7c could induce cancer cells apoptosis and have less cytotoxicity in normal human cell. Further investigations on Hela cells revealed that 7c could also induce ROS generation, lysosome rupture as well as cathepsin B release. Subsequent mitochondrial damages including mitochondrial membrane permeabilization and the release of cytochrome c were also found in 7c when treating with Hela cells. According to our data, 7c may act as a lead compound for potential anticancer drugs. The idea of naphthalimides modification may also provide a novel strategy for naphthalimides design.
authors: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237, PR China.
authors: Ke
authors: K
authors: Shen
authors: Liyun
authors: L
authors: Sun
authors: Huanying
authors: H
authors: Zhang
authors: Yufang
authors: Y
authors: Xu
authors: Xuhong
authors: X
authors: Qian
authors: Yanhua
authors: Y
authors: Lu
authors: Qi
authors: Q
authors: Li
authors: Lei
authors: L
authors: Ni
authors: Jianwen
authors: J
authors: Liu
mesh_terms: D000225:Adenine; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D053644:Naphthalimides / Q000737:chemistry* / Q000494:pharmacology; D063065:Organophosphonates; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D053644:Naphthalimides; D063065:Organophosphonates; D017382:Reactive Oxygen Species; C037020:amonafide; D000225:Adenine