title: The effects of a plant proteinase inhibitor from Enterolobium contortisiliquum on human tumor cell lines.
abstract: Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (K(iapp)=4.3 nM) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogen-induced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concentration range of 1.0-2.5 μM rather specifically tumor cell viability without targeting primary fibroblasts and hMSCs. Taken together, our data indicate that the polyspecific proteinase inhibitor EcTI prevents proMMP activation and is cytotoxic against tumor cells without affecting normal tissue remodeling fibroblasts or regenerative hMSCs being an important tool in the studies of tumor cell development and dissemination.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Três de Maio 100, 04044-020, São Paulo, SP, Brazil.
authors.forename: Adriana Miti
authors.initials: AM
authors.lastname: Nakahata
authors.forename: Barbara
authors.initials: B
authors.lastname: Mayer
authors.forename: Christian
authors.initials: C
authors.lastname: Ries
authors.forename: Cláudia Alessandra Andrade
authors.initials: CA
authors.lastname: de Paula
authors.forename: Marisa
authors.initials: M
authors.lastname: Karow
authors.forename: Peter
authors.initials: P
authors.lastname: Neth
authors.forename: Misako U
authors.initials: MU
authors.lastname: Sampaio
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Maria Luiza V
authors.initials: ML
authors.lastname: Oliva
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D010940:Plant Proteins / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D010940:Plant Proteins; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010958:Plasminogen; D019272:Leukocyte Elastase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D013755:Tetradecanoylphorbol Acetate