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Investigating the role of dynein in the mechanism of antitumor action of Amblyomin-X in melanoma cells and pancreatic adenocarcinoma

Grant number: 11/05969-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2011
Effective date (End): April 30, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Marisa Chudzinski-Tavassi
Grantee:Mario Thiego Fernandes Pacheco
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Hematophagous animals are sources of natural anticoagulants, since, for food, they need to keep the blood in their digestive tract. The saliva of the star tick (Amblyomma cajennense) of spotted fever transmitter contains a number of physiologically active molecules that can participate in diverse biological processes such as coagulation and fibrinolysis, immunity, inflammation and angiogenesis. From the construction of a cDNA library from salivary glands of Amblyomma cajennense identified a transcript that encodes a protease inhibitor Kunitz type. The protein isolated and produced in recombinant form, called X-amblyomin have anticoagulant properties similar to endogenous inhibitor TFPI with FXa inhibitory effect factor, prolonging blood clotting. Knowing the relationship between cancer, coagulation, apoptosis, angiogenesis, and genetic factor involved in metastasis, it was found that the recombinant protein also has pro-apoptotic effects selective for tumor cells as well as anti-angiogenic activity and regression of tumor mass and metastases in some tumors. Among the activities described focus on the substance, there is its ability to inhibit the proteasome leading to apoptosis. If the capacity of the proteasome is overwhelmed or exhausted, he damaged proteins called aggregates degraded form aggresomes, which are transported by a network of microtubules by motor proteins, especially the dynein. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORAIS, KATIA L. P.; FERNANDES PACHECO, MARIO THIEGO; BERRA, CAROLINA MARIA; BOSCH, ROSEMARY V.; SCIANI, JULIANA MOZER; CHAMMAS, ROGER; SAITO, RENATA DE FREITAS; IQBAL, ASIF; CHUDZINSKI-TAVASSI, ANA MARISA. Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell. Molecular and Cellular Biochemistry, v. 415, n. 1-2, p. 119-131, APR 2016. Web of Science Citations: 7.
CHUDZINSKI-TAVASSI, ANA MARISA; MORAIS, KATIA L. P.; FERNANDES PACHECO, MARIO THIEGO; MESQUITA PASQUALOTO, KERLY FERNANDA; DE SOUZA, JEAN GABRIEL. Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates. BIOMEDICINE & PHARMACOTHERAPY, v. 77, p. 14-19, FEB 2016. Web of Science Citations: 8.
PACHECO, MARIO T. F.; MORAIS, KATIA L. P.; BERRA, CAROLINA M.; DEMASI, MARILENE; SCIANI, JULIANA M.; BRANCO, VANIA G.; BOSCH, ROSEMARY V.; IQBAL, ASIF; CHUDZINSKI-TAVASSI, ANA MARISA. Specific role of cytoplasmic dynein in the mechanism of action of an antitumor molecule, Amblyomin-X. Experimental Cell Research, v. 340, n. 2, p. 248-258, JAN 15 2016. Web of Science Citations: 7.
PACHECO, MARIO T. F.; BERRA, CAROLINA M.; MORAIS, KATIA L. P.; SCIANI, JULIANA M.; BRANCO, VANIA G.; BOSCH, ROSEMARY V.; CHUDZINSKI-TAVASSI, ANA M. Dynein Function and Protein Clearance Changes in Tumor Cells Induced by a Kunitz-Type Molecule, Amblyomin-X. PLoS One, v. 9, n. 12 DEC 5 2014. Web of Science Citations: 13.
MORAIS, KATIA L. P.; MESQUITA PASQUALOTO, KERLY FERNANDA; FERNANDES PACHECO, MARIO THIEGO; BERRA, CAROLINA MARIA; ALVAREZ-FLORES, MIRYAM PAOLA; CHUDZINSKI-TAVASSI, ANA MARISA. Rational development of a novel TFPI-like inhibitor from Amblyomma cajennense tick. Toxin Reviews, v. 33, n. 1-2, SI, p. 48-52, MAR-JUN 2014. Web of Science Citations: 3.

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