Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and ROS production

2012; Springer Science+Business Media; Volume: 31; Issue: 3 Linguagem: Inglês

10.1007/s10637-012-9871-1

1573-0646

Durvanei Augusto Maria, Jean Gabriel de Souza, Kátia L.P. Morais, Carolina Maria Berra, Hamilton de Campos Zampolli, Marilene Demasi, Simone Michaela Simons, Renata de Freitas Saito, Roger Chammas, Ana Marisa Chudzinski‐Tavassi,

Mitochondrial Function and Pathology

In cancer-treatment, potentially therapeutic drugs trigger their effects through apoptotic mechanisms. Generally, cell response is manifested by Bcl-2 family protein regulation, the impairment of mitochondrial functions, and ROS production. Notwithstanding, several drugs operate through proteasome inhibition, which, by inducing the accumulation and aggregation of misfolded or unfolded proteins, can lead to endoplasmic reticulum (ER) stress. Accordingly, it was shown that Amblyomin-X, a Kunitz-type inhibitor identified in the transcriptome of the Amblyomma cajennense tick by ESTs sequence analysis of a cDNA library, obtained in recombinant protein form, induces apoptosis in murine renal adenocarcinoma (RENCA) cells by: inducing imbalance between pro- and anti-apoptotic Bcl-2 family proteins, dysfunction/mitochondrial damage, production of reactive oxygen species (ROS), caspase cascade activation, and proteasome inhibition, all ER-stress inductive. Moreover, there was no manifest action on normal mouse-fibroblast cells (NHI3T3), suggesting an Amblyomin-X tumor-cell selectivity. Taken together, these evidences indicate that Amblyomin-X could be a promising candidate for cancer therapy.