title: Recombinant Multivalent EMMPRIN Extracellular Domain Induces U937 Human Leukemia Cell Apoptosis by Downregulation of Monocarboxylate Transporter 1 and Activation of Procaspase-9.
abstract: This study was carried out to understand the effect of the recombinant multivalent extracellular matrix metalloproteinase inducer (EMMPRIN) extracellular domain, designated as rmEMMPRINex, on the apoptotic cell death of human leukemia U937 cells. Expression of monocarboxylate transporter 1 (MCT1) and caspase-9 in U937 treated with rmEMMPRINex was investigated in this study. Levels of membrane MCT1 and intracellular procaspase-9 were decreased in rmEMMPRINex-treated cells in comparison to controls. However, the expression of activated caspase-9 was undetectable. rmEMMPRINex also induced DNA fragmentation and apoptosis in U937 cells. Taken together, we concluded that interaction of rmEMMPRINex with U937 cells leads to inhibition of MCT1 membrane expression, intracellular activation of procaspase-9, followed by DNA fragmentation and apoptosis. This may contribute to the conceptual development of novel cancer drugs in the future.
authors.affiliation: Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 110 Intawaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand, nutjeera.in@cmu.ac.th.
authors.forename: Nutjeera
authors.initials: N
authors.lastname: Intasai
authors.forename: Supansa
authors.initials: S
authors.lastname: Pata
authors.forename: Khajornsak
authors.initials: K
authors.lastname: Tragoolpua
authors.forename: Chatchai
authors.initials: C
authors.lastname: Tayapiwatana
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051926:Basigin / Q000235:genetics / Q000494:pharmacology*; D053453:Caspase 9 / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D027981:Symporters / Q000096:biosynthesis*; D020298:U937 Cells; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D051926:Basigin; D053453:Caspase 9; D027501:Monocarboxylic Acid Transporters; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C506433:CASP9 protein, human