title: Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import.
abstract: Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys(38) to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Yangling
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: liuxuejiao0923@126.com.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China; Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: lihmd@163.com.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D004148:Dioxolanes / Q000494:pharmacology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D021381:Protein Transport; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D051996:Transcription Factor RelA; C498077:piperlongumine; D010881:Piperidones
keywords: ABC-DLBCL; NF-κB; Nuclear import; Piperlongumine; p65