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Influence of protein phosphatases inhibitors in the expression and / or activity of protein kinases in pancreatic cancer

Grant number: 12/24385-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2013
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Karin Juliane Pelizzaro Rocha
Grantee:Marina Pereira Dias
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:09/51602-5 - Chemical biology: new natural and synthetic molecular targets against cancer, structural studies, biological evaluation and mode of action, AP.TEM

Abstract

Pancreatic cancer is extremely aggressive and with poor prognosis, due to delayed diagnosis, which compromises the effectiveness of treatment. Thus, more information about the biology of this tumor is essential for identifying targets for treatment, defining markers to diagnosis and developing new drugs. Our research group has been collaborating in a thematic project that aims to synthetize protein tyrosine phosphatases inhibitors and consequently employs them as antitumoral agents. So far, six compounds derived from goniotalamina and pirplatin, and one derivative of the RK682, the RPV10, inhibited protein tyrosine phosphatases (as demonstrated in kinetic experiments with recombinant enzymes) and showed a strong toxic effect on cells of pancreatic cancer. Taking in mind that protein phosphatases and protein kinases play important cellular functions through dephosphorylation/transient phosphorylation of proteins, and that the activity of both classes of enzymes are tightly regulated, the main goal of this project is to evaluate the influence of phosphatases inhibitors on the expression and/or activity of protein kinases such as receptor (Axl), cytoplasmic (Akt and ERK p42/44) and nuclear (CDKs) in pancreatic cancer cells. Moreover, it will also be assessed the effect of these compounds on cell adhesion and migration of pancreatic cancer cells. It is noteworthy that protein kinases are important for the survival and proliferation of pancreatic tumor aggressiveness. Therefore, this study will bring out relevant information about the influence of inhibitors of protein phosphatase on protein kinases and also aids to define the antitumor mechanism of these compounds.(AU)

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Scientific publications
(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)
BARCELOS, ROSIMEIRE COURA; PELIZZARO-ROCHA, KARIN JULIANE; PASTRE, JULIO CEZAR; DIAS, MARINA PEREIRA; FERREIRA-HALDER, CARMEN VERISSIMA; ALOISE PILLI, RONA IDO. A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 87, p. 745-758, . (10/15496-3, 10/16990-1, 09/51602-5, 12/24385-6)
TONETO NOVAES, LUIZ FERNANDO; AVILA, CAROLINA MARTINS; PELIZZARO-ROCHA, KARIN JULIANE; VENDRAMINI-COSTA, DEBORA BARBOSA; DIAS, MARINA PEREIRA; BARBOSA TRIVELLA, DANIELA BARRETO; DE CARVALHO, JOAO ERNESTO; FERREIRA-HALDER, CARMEN VERISSIMA; PILLI, RONALDO ALOISE. (-)-Tarchonanthuslactone: Design of New Analogues, Evaluation of their Antiproliferative Activity on Cancer Cell Lines, and Preliminary Mechanistic Studies. CHEMMEDCHEM, v. 10, n. 10, p. 1687-1699, . (10/08673-6, 13/08896-3, 10/17544-5, 12/24385-6, 12/09254-2, 09/51602-5)

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