Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model

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Arquivos
art_SOUZA_Promising_pharmacological_profile_of_a_Kunitztype_inhibitor_in_2016.PDF (3.43 MB)
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2016
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
IMPACT JOURNALS LLC
Autores
SOUZA, Jean Gabriel de
MORAIS, Katia L. P.
ANGLES-CANO, Eduardo
BOUFLEUR, Pamela
MARIA, Durvanei Augusto
ORIGASSA, Clarice Silvia Taemi
ZAMPOLLI, Hamilton de Campos
CAMARA, Niels Olsen Saraiva
BERRA, Carolina Maria
Citação
ONCOTARGET, v.7, n.38, p.62255-62266, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Renal cell carcinoma (RCC), also called kidney cancer or renal adenocarcinoma, is highly resistant to current treatments. It has been previously reported that a Kunitz-type inhibitor domain-containing protein, isolated from the salivary glands of the Amblyomma cajennense tick, triggers apoptosis in murine renal adenocarcinoma cells (Renca) by inhibiting the proteasome and endoplasmic reticulum stress. Of note, Amblyomin-X is the corresponding recombinant protein identified in the cDNA library from A. cajennense salivary glands. Herein, using orthotopic kidney tumors in mice, we demonstrate that Amblyomin-X is able to drastically reduce the incidence of lung metastases by inducing cell cycle arrest and apoptosis. The in vitro assays show that Amblyomin-X is capable of reducing the proliferation rate of Renca cells, promoting cell cycle arrest, and down-regulating the expression of crucial proteins (cyclin D1, Ki67 and Pgp) involved in the aggressiveness and resistance of RCC. Regarding non-tumor cells (NIH3T3), Amblyomin-X produced minor effects in the cyclin D1 levels. Interestingly, observing the image assays, the fluorescence-labelled Amblyomin-X was indeed detected in the tumor stroma whereas in healthy animals it was rapidly metabolized and excreted. Taken the findings together, Amblyomin-X can be considered as a potential anti-RCC drug candidate.
Palavras-chave
renal cell carcinoma, amblyomin-X, antitumor activity, tumor resistance, tumor affinity
URI
https://observatorio.fm.usp.br/handle/OPI/17171
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - ODS/03