title: 7-b, a novel amonafide analogue, cause growth inhibition and apoptosis in Raji cells via a ROS-mediated mitochondrial pathway.
abstract: Previous studies have shown that 7-b (6-(dodecylamino)-2-(3-(4-methylpiperazin-1-yl)propyl)-1H-benzo-[de]isoquinoline-1,3(2H)-dione), a novel amonafide-based DNA intercalator, was generated as a new anticancer candidate. However, the effects induced by 7-b and the molecular mechanisms involved remain poorly understood in Burkitt's lymphoma. To shed light on these issues, we have investigated the effects of 7-b on proliferation, cell cycle progression, apoptosis activity and oxidative stress levels of lymphoma Raji cells in vitro. Our results showed that 7-b inhibited the proliferation of Raji cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, 7-b treatment triggered programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (Δψm). Altogether our results showed that 7-b mediated its growth inhibitory effects on Raji cells via the activation of a ROS-mediated mitochondrial pathway and cell cycle checkpoint signaling pathway which subsequently targeted p21.
authors.affiliation: 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, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Lin
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
authors.forename: Huanying
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
mesh_terms: D000225:Adenine; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D053644:Naphthalimides / Q000737:chemistry / Q000494:pharmacology*; D009336:Necrosis; D063065:Organophosphonates; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C558824:6-(dodecylamino)-2-(3-(4-methylpiperazin-1-yl)propyl)-1H-benzo-(de)isoquinoline-1,3(2H)-dione; D000970:Antineoplastic Agents; D053644:Naphthalimides; D063065:Organophosphonates; D017382:Reactive Oxygen Species; C037020:amonafide; D000225:Adenine