Oncotarget

Research Papers:

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

Jean Gabriel de Souza, Katia L.P. Morais, Eduardo Anglés-Cano, Pamela Boufleur, Evandro Sobroza de Mello, Durvanei Augusto Maria, Clarice Silvia Taemi Origassa, Hamilton de Campos Zampolli, Niels Olsen Saraiva Câmara, Carolina Maria Berra, Rosemary Viola Bosch, Ana Marisa Chudzinski-Tavassi _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2016; 7:62255-62266. https://doi.org/10.18632/oncotarget.11555

Metrics: PDF 490 views  |   HTML 526 views  |   ?  


Abstract

Jean Gabriel de Souza1,2,3, Katia L.P. Morais1,3, Eduardo Anglés-Cano4, Pamela Boufleur1,2, Evandro Sobroza de Mello5, Durvanei Augusto Maria1, Clarice Silvia Taemi Origassa6, Hamilton de Campos Zampolli7, Niels Olsen Saraiva Câmara6,8, Carolina Maria Berra1, Rosemary Viola Bosch1, Ana Marisa Chudzinski-Tavassi1,3

1Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil

2Department of Biochemistry, Federal University of São Paulo, SP, Brazil

3CENTD- Center of Excellence in New Target Discovery, Butantan Institute, SP, Brazil

4INSERM UMR_S 1140-Université Paris Descartes, Sorbonne Paris Cité, Paris, France

5Department of Pathology, University of Sao Paulo Medical School, SP, Brazil

6Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, SP, Brazil

7Division of Urology, Arnaldo Vieira de Carvalho Cancer Institute, SP, Brazil

8Nephrology Division, Federal University of São Paulo, SP, Brazil

Correspondence to:

Ana Marisa Chudzinski-Tavassi, email: ana.chudzinski@butantan.gov.br

Keywords: renal cell carcinoma, amblyomin-X, antitumor activity, tumor resistance, tumor affinity

Received: May 23, 2016     Accepted: August 13, 2016     Published: August 23, 2016

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 11555