title: Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma.
abstract: This study investigated the cytotoxic effect of oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, in human diffuse large B cell lymphoma (DLBCL) in vitro and in vivo and the potential molecular mechanisms for ORI-induced cell apoptosis. ORI treatment caused reactive oxygen species (ROS)-mediated oxidative DNA damage response (DDR) and the c-Jun N-terminal kinase (JNK) pathway activation, leading to an induction of intrinsic apoptosis. ROS abolition blocked ORI-induced apoptosis and attenuated the expression of phospho-histone H2AX and phospho-JNK, indicating that ROS-mediated DNA damage and JNK pathway activation were involved in ORI-induced apoptosis. The systemic administration of ORI suppressed the growth of human DLBCL xenografts without showing significant toxicity. These findings suggest that ORI may have promising therapeutic application in DLBCL.
authors.affiliation: a Department of Laboratory Medicine , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , PR China ;|b Department of Hematology , Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine , Shanghai , PR China.
authors.forename: Zi-Zhen
authors.initials: ZZ
authors.lastname: Xu
authors.affiliation: b Department of Hematology , Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine , Shanghai , PR China.
authors.forename: Wan-Bin
authors.initials: WB
authors.lastname: Fu
authors.affiliation: b Department of Hematology , Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine , Shanghai , PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jin
authors.affiliation: b Department of Hematology , Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine , Shanghai , PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Guo
authors.affiliation: b Department of Hematology , Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine , Shanghai , PR China.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Wang
authors.affiliation: a Department of Laboratory Medicine , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , PR China ;
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004249:DNA Damage; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D006657:Histones; D017382:Reactive Oxygen Species; C011959:oridonin
keywords: Apoptosis; DNA damage response; JNK; diffuse large B cell lymphoma; oridonin; reactive oxygen species