title: A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system.
abstract: The aim of this study was to evaluate the anti-tumor activity of Amblyomin-X, a serine protease Kunitz-type inhibitor. Amblyomin-X induced tumor mass regression and decreased number of metastatic events in a B16F10 murine melanoma model. Alterations on expression of several genes related to cell cycle were observed when two tumor cell lines were treated with Amblyomin-X. PSMB2, which encodes a proteasome subunit, was differentially expressed, in agreement to inhibition of proteasomal activity in both cell lines. In conclusion, our results indicate that Amblyomin-X selectively acts on tumor cells by inducing apoptotic cell death, possibly by targeting the ubiquitin-proteasome system.
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av. Vital Brazil 1500, 05503-900, São Paulo SP, Brazil. amchudzinski@butantan.gov.br
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Chudzinski-Tavassi
authors.forename: Paulo Luis
authors.initials: PL
authors.lastname: De-Sá-Júnior
authors.forename: Simone Michaela
authors.initials: SM
authors.lastname: Simons
authors.forename: Durvanei Augusto
authors.initials: DA
authors.lastname: Maria
authors.forename: Janaina
authors.initials: J
authors.lastname: de Souza Ventura
authors.forename: Isabel de Fátima Correia
authors.initials: IF
authors.lastname: Batista
authors.forename: Fernanda
authors.initials: F
authors.lastname: Faria
authors.forename: Esther
authors.initials: E
authors.lastname: Durães
authors.forename: Eduardo Moraes
authors.initials: EM
authors.lastname: Reis
authors.forename: Marilene
authors.initials: M
authors.lastname: Demasi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D060829:Arthropod Proteins; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D026863:Ixodidae / Q000737:chemistry* / Q000235:genetics; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C559369:Amblyomin-X protein, Amblyomma cajennense; D000970:Antineoplastic Agents; D060829:Arthropod Proteins; D012471:Salivary Proteins and Peptides; D015842:Serine Proteinase Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex