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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

2010; Elsevier BV; Volume: 56; Issue: 7 Linguagem: Inglês

10.1016/j.toxicon.2010.04.019

1879-3150

Ana Marisa Chudzinski‐Tavassi, Paulo Luis De-Sá-Júnior, Simone Michaela Simons, Durvanei Augusto Maria, Janaína de Souza Ventura, Isabel de Fátima Correia Batista, Fernanda Faria, Esther de Oliveira Durães, Eduardo M. Reis, Marilene Demasi,

Protease and Inhibitor Mechanisms

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.