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Título: A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and ROS production
Autor: MARIA, Durvanei AugustoSOUZA, Jean Gabriel deMORAIS, Katia L. P.BERRA, Carolina MariaZAMPOLLI, Hamilton de CamposDEMASI, MarileneSIMONS, Simone MichaelaSAITO, Renata de FreitasCHAMMAS, RogerCHUDZINSKI-TAVASSI, Ana Marisa
Citación: INVESTIGATIONAL NEW DRUGS, v.31, n.3, p.493-505, 2013
Resumen: 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.
Aparece en las colecciones:

Artigos e Materiais de Revistas Científicas - FM/MDR
Departamento de Radiologia - FM/MDR

Artigos e Materiais de Revistas Científicas - LIM/24
LIM/24 - Laboratório de Oncologia Experimental

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


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