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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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de Souza, Jean Gabriel ; Morais, Katia L. P. ; Angles-Cano, Eduardo ; Boufleur, Pamela ; de Mello, Evandro Sobroza ; Maria, Durvanei Augusto ; Taemi Origassa, Clarice Silvia ; Zampolli, Hamilton de Campos ; Saraiva Camara, Niels Olsen ; Berra, Carolina Maria ; Bosch, Rosemary Viola ; Chudzinski-Tavassi, Ana Marisa
Total Authors: 12
Document type: Journal article
Source: ONCOTARGET; v. 7, n. 38, p. 62255-62266, SEP 20 2016.
Web of Science Citations: 6
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. (AU)

FAPESP's process: 12/06944-8 - Effect of Amblyomin-X at interface of the immune system and hemostasis during progression RENCA tumor (murine renal cell carcinoma): in vivo and in vitro
Grantee:Jean Gabriel de Souza
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/07958-7 - EVALUATION OF THE PRO-APOPTOTIC MECHANISM OF ACTION OF THE AMBLYOMIN-X
Grantee:Kátia Luciano Pereira Morais
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
Grantee:Ana Marisa Chudzinski-Tavassi
Support type: Research Grants - Research Centers in Engineering Program