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

Autor:	de Souza JG; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.; Department of Biochemistry, Federal University of São Paulo, SP, Brazil.; CENTD- Center of Excellence in New Target Discovery, Butantan Institute, SP, Brazil., Morais KL; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.; CENTD- Center of Excellence in New Target Discovery, Butantan Institute, SP, Brazil., Anglés-Cano E; INSERM UMR_S 1140-Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Boufleur P; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.; Department of Biochemistry, Federal University of São Paulo, SP, Brazil., de Mello ES; Department of Pathology, University of Sao Paulo Medical School, SP, Brazil., Maria DA; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil., Origassa CS; Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, SP, Brazil., de Campos Zampolli H; Division of Urology, Arnaldo Vieira de Carvalho Cancer Institute, SP, Brazil., Câmara NO; Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, SP, Brazil.; Nephrology Division, Federal University of São Paulo, SP, Brazil., Berra CM; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil., Bosch RV; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil., Chudzinski-Tavassi AM; Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.; CENTD- Center of Excellence in New Target Discovery, Butantan Institute, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2016 Sep 20; Vol. 7 (38), pp. 62255-62266.
DOI:	10.18632/oncotarget.11555
Abstrakt:	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. Competing Interests: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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