title: Brefeldin A exerts differential effects on anaplastic lymphoma kinase positive anaplastic large cell lymphoma and classical Hodgkin lymphoma cell lines.
abstract: To obtain further insights into the biological differences of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL) and classical Hodgkin lymphoma (HL), we screened microbial culture filtrates to search for compounds that would exert a significantly greater effect on the viability of ALK+ ALCL cell lines compared to HL cell lines and identified Brefeldin A (BFA) as a suitable candidate. BFA inhibited phosphorylation of ALK and its downstream molecule, signal transducer and activator of transcription 3 (STAT3), one of the central pathways for the survival of ALK+ ALCL cells. In HL cell lines BFA did not affect CD30 expression or constitutive nuclear factor (NF)-κB activity, both of which are critical for HL cell survival. BFA induced disruption of the Golgi apparatus in ALK+ ALCL cell lines, which was accompanied by a decrease in active ADP-ribosylation factor 1 (ARF1), whereas BFA had no significant effect on these parameters in HL cell lines. These results add extra insights into the biological distinction between ALK+ ALCL and HL cells and highlight the Golgi apparatus as a target for the treatment of ALK+ ALCL.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Kanagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
authors.affiliation: Department of Haematology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Kanagawa, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kawato
authors.affiliation: Boston University School of Medicine and Department of Dermatology and Skin Surgery, Roger Williams Medical Center, Providence, RI, USA.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.affiliation: Department of Haematology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.affiliation: Bioscience Institute, Meiji Seika Pharma Co. Ltd., Kanagawa, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kunisada
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Haematology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Horie
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000037:antagonists & inhibitors; D000077548:Anaplastic Lymphoma Kinase; D020126:Brefeldin A / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006056:Golgi Apparatus / Q000187:drug effects; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors
chemical_list: D017730:Ki-1 Antigen; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D020126:Brefeldin A; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D020823:ADP-Ribosylation Factor 1
keywords: Brefeldin A; STAT3; anaplastic large cell lymphoma; anaplastic lymphoma kinase; classical Hodgkin lymphoma