| Full text | |
| Author(s): Show less - |
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: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| 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 Opportunities: | Research Grants - Research Centers in Engineering Program |
| 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 Opportunities: | Research Projects - Thematic Grants |
| 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 Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 10/07958-7 - EVALUATION OF THE PRO-APOPTOTIC MECHANISM OF ACTION OF THE AMBLYOMIN-X |
| Grantee: | Kátia Luciano Pereira Morais |
| Support Opportunities: | Scholarships in Brazil - Doctorate |