Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation

• Published in: Cancer letters 2015-01, Vol.356 (2), p.994-1006
• Main Authors: Kiss, Izabella, Unger, Christine, Huu, Chi Nguyen, Atanasov, Atanas Georgiev, Kramer, Nina, Chatruphonprasert, Waranya, Brenner, Stefan, McKinnon, Ruxandra, Peschel, Andrea, Vasas, Andrea, Lajter, Ildiko, Kain, Renate, Saiko, Philipp, Szekeres, Thomas, Kenner, Lukas, Hassler, Melanie R, Diaz, Rene, Frisch, Richard, Dirsch, Verena M, Jäger, Walter, de Martin, Rainer, Bochkov, Valery N, Passreiter, Claus M, Peter-Vörösmarty, Barbara, Mader, Robert M, Grusch, Michael, Dolznig, Helmut, Kopp, Brigitte, Zupko, Istvan, Hohmann, Judit, Krupitza, Georg
• Format: Article
• Language: English
• Subjects: 3D-compound testing; ALCL; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Asteraceae - chemistry; Blotting, Western; Caspases - genetics; Caspases - metabolism; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Endothelium, Lymphatic - drug effects; Endothelium, Lymphatic - pathology; Hematology, Oncology and Palliative Medicine; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Lobatin; Lymphendothelial intravasation; Lymphoma, Large-Cell, Anaplastic - drug therapy; Lymphoma, Large-Cell, Anaplastic - metabolism; Lymphoma, Large-Cell, Anaplastic - pathology; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Neoplasm Invasiveness; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; NPM/ALK; Plant Extracts - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Sesquiterpenes - pharmacology; Tumor Cells, Cultured
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2014.11.019

Highlights • Lobatin B inhibited NPM/ALK protein expression at the transcriptional level. • Consequently, the cascade of downstream signalling to JunB and PDGFR-β was down-regulated. • Importantly, Lobatin B was toxic to ALCL and leukaemia cell lines but not to normal PBMCs. • Therefore, Lobatin B may serve as lead for novel concepts for more specific treatment of NPM/ALK positive ALCL. • Furthermore, Lobatin B inhibited NF-κB and the intravasation of tumour spheroids through the lymph-endothelial barrier.