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Antitumor and apoptotic effects of peptides obtained from bovine b-casein INKKI and YPVPQFTE and its analogues and mastoparanes isolated from wasp venoms in experimental melanome models in vitro and in vivo

Grant number: 10/51077-5
Support Opportunities:Regular Research Grants
Duration: December 01, 2010 - November 30, 2012
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Ivo Lebrun
Grantee:Ivo Lebrun
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Melanoma is a neoplasic disease characterized by the uncontrolled proliferation of melanoblasts the precursor cells of melanocytes that are responsible for the skin pigmentation. Melanoma represents only 4% of the cancer types but is considered dangerous because its high metastatic capacity. It could occur in all surface of the skin or ungueal structures and even in areas not direct exposed to the sunlight such as eyes, mucosa (mouth and genitals) or internal organs (ELLERHORST et al., 2004). Proteolytic digestion products obtained from different foods or from endogenous macromolecules besides the organism supply for essential aminoacids and organic nitrogen are able to generate several bioactive peptides that in the last decades were been studied and characterized in many biological systems (SCHLINME; MEISEL, 1995; for revision see PIMENTA and LEBRUN, 2007). Previous studies developed in the Biochemistry and Biophysics Laboratory isolated, characterized and synthesized the peptides INKKI e YPVEPFTE. The first one showed a Bradykinin potentiating activity, increasing in 80% the fagocityc activity of mice peritoneal resident macrophages and increasing in the H2O2 release by macrophages (LEBRUN et al. 2004); besides the second showed a high Bradykinin potentiating activity towards a mechanism that is not related to the angiotensin converting (LEBRUN et al., 1995). Recently it was verified that these peptides acts on melanoma tumor cells without affecting normal ones (AZEVEDO, RA, Master of Science thesis, AZEVEDO RA et al, submitted) it was also observed a significant reduction in tumor in "in vivo" animal models. The present project will study the distribution of the tumoral cells based on cell cycle expression caspase-3, 8, 9, Ki67, PCNA, Ciclina D1, Bcl-2 using flow citometry and establishing the proportion of death by necrosis or apoptosis Anexin V/PI; and variations on the mitochondrial potential in vitro e in vivo e before and after the treatment with the casein peptides it analogues and mastoparans to better understand the action of these peptides on melanoma. (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)
DE AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; FERREIRA, ADILSON K.; MATSUO, ALISSON L.; MASSAOKA, MARIANA H.; GIROLA, NATALIA; AUADA, ALINE V. V.; FARIAS, CAMYLA F.; PASQUALOTO, KERLY F. M.; RODRIGUES, CECILIA P.; et al. Mastoparan induces apoptosis in B1 6F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo. Peptides, v. 68, p. 113-119, . (10/51077-5)

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