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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.
AuthorsAna Marisa Chudzinski-Tavassi, Paulo Luis De-Sá-Júnior, Simone Michaela Simons, Durvanei Augusto Maria, Janaina de Souza Ventura, Isabel de Fátima Correia Batista, Fernanda Faria, Esther Durães, Eduardo Moraes Reis, Marilene Demasi
JournalToxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 56 Issue 7 Pg. 1145-54 (Dec 15 2010) ISSN: 1879-3150 [Electronic] England
PMID20570593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Amblyomin-X protein, Amblyomma cajennense
  • Antineoplastic Agents
  • Arthropod Proteins
  • Salivary Proteins and Peptides
  • Serine Proteinase Inhibitors
  • Ubiquitin
  • Proteasome Endopeptidase Complex
Topics
  • Animals
  • Antineoplastic Agents (chemistry, isolation & purification, therapeutic use)
  • Apoptosis (drug effects)
  • Arthropod Proteins
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Ixodidae (chemistry, genetics)
  • Melanoma, Experimental (drug therapy, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Proteasome Endopeptidase Complex (drug effects, metabolism)
  • Salivary Glands (chemistry)
  • Salivary Proteins and Peptides (chemistry, isolation & purification, therapeutic use)
  • Serine Proteinase Inhibitors (chemistry, isolation & purification, therapeutic use)
  • Ubiquitin (metabolism)

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