Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model
| Autor: | Carolina Maria Berra, Ana Marisa Chudzinski-Tavassi, Evandro Sobroza de Mello, Katia L.P. Morais, Niels Olsen Saraiva Câmara, Clarice Silvia Taemi Origassa, Eduardo Anglés-Cano, Rosemary Viola Bosch, Jean Gabriel de Souza, Hamilton de Campos Zampolli, Pamela Boufleur, Durvanei Augusto Maria |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Nephrology Apoptosis Kidney Amblyomma cajennense Mice 0302 clinical medicine Renal cell carcinoma Cyclin D1 tumor affinity Mice Inbred BALB C biology Endoplasmic Reticulum Stress Kidney Neoplasms Recombinant Proteins medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Oncology 030220 oncology & carcinogenesis Proteasome Inhibitors Research Paper Proteasome Endopeptidase Complex renal cell carcinoma medicine.medical_specialty Down-Regulation Arthropod Proteins 03 medical and health sciences Cell Line Tumor Internal medicine Toxicity Tests medicine Animals Humans antitumor activity ATP Binding Cassette Transporter Subfamily B Member 1 Salivary Proteins and Peptides Carcinoma Renal Cell Cancer amblyomin-X Cell Cycle Checkpoints biology.organism_classification medicine.disease Xenograft Model Antitumor Assays tumor resistance Transplantation Ki-67 Antigen 030104 developmental biology Immunology NIH 3T3 Cells Cancer research Kidney cancer |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11555 |
| Popis: | // Jean Gabriel de Souza 1, 2, 3 , Katia L.P. Morais 1, 3 , Eduardo Angles-Cano 4 , Pamela Boufleur 1, 2 , Evandro Sobroza de Mello 5 , Durvanei Augusto Maria 1 , Clarice Silvia Taemi Origassa 6 , Hamilton de Campos Zampolli 7 , Niels Olsen Saraiva Câmara 6, 8 , Carolina Maria Berra 1 , Rosemary Viola Bosch 1 , Ana Marisa Chudzinski-Tavassi 1, 3 1 Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil 2 Department of Biochemistry, Federal University of Sao Paulo, SP, Brazil 3 CENTD- Center of Excellence in New Target Discovery, Butantan Institute, SP, Brazil 4 INSERM UMR_S 1140-Universite Paris Descartes, Sorbonne Paris Cite, Paris, France 5 Department of Pathology, University of Sao Paulo Medical School, SP, Brazil 6 Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of Sao Paulo, SP, Brazil 7 Division of Urology, Arnaldo Vieira de Carvalho Cancer Institute, SP, Brazil 8 Nephrology Division, Federal University of Sao 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. |
| Databáze: | OpenAIRE |
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