Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/90202
Type: Artigo de periódico
Title: Effects Of P-mapa Immunomodulator On Toll-like Receptors And P53:potential Therapeutic Strategies For Infectious Diseases And Cancer
Author: Favaro W.J.
Nunes O.S.
Seiva F.R.F.
Nunes I.S.
Woolhiser L.K.
Duran N.
Lenaerts A.J.
Abstract: Background: Compounds that can act as agonists for toll-like receptors (TLRs) may be promising candidates for the development of drugs against infectious diseases and cancer. The present study aimed to characterize the immunomodulatory effects of P-MAPA on TLRs in vitro and in vivo, as well as to investigate its potential as adjuvant therapy in infectious diseases and cancer. Methods: For these purposes, the activity of P-MAPA on TLRs was assayed in vitro through NF-κB activation in HEK293 cells expressing a given TLR, and using an in vivo animal model for bladder cancer (BC). The antimicrobial activity of P-MAPA was tested against Mycobacterium tuberculosis (TB) in vitro in an MIC assay, and in vivo using an aerosol infection model of murine tuberculosis. Antitumor effects of P-MAPA were tested in an animal model with experimentally induced BC. Moxifloxacin (MXF) and Bacillus Calmette-Guerin (BCG) were used as positive controls in the animal models. Results: The results showed that P-MAPA, administered alone or in combination with MXF, induced significant responses in vivo against TB. In contrast, the compound did not show antimicrobial activity in vitro. P-MAPA showed a significant stimulatory effect on human TLR2 and TLR4 in vitro. In BC, TLR2, TLR4 and p53 protein levels were significantly higher in the P-MAPA group than in the BCG group. The most common histopathological changes in each group were papillary carcinoma in BC group, low-grade intraepithelial neoplasia in BCG group and simple hyperplasia in P-MAPA group. Concerning the toxicological analysis performed during BC treatment, P-MAPA did not show evidence for hepatotoxicity and nephrotoxicity. Conclusions: In conclusion, P-MAPA acted as TLR ligand in vitro and improved the immunological status in BC, increasing TLR2 and TLR4 protein levels. P-MAPA immunotherapy was more effective in restoring p53 and TLRs reactivities and showed significantly greater antitumor activity than BCG. The activation of TLRs and p53 may provide a hypothetical mechanism for the therapeutic effects in both cancer and infectious diseases. Taken together data obtained will encourage the further investigation of P-MAPA as a potential candidate for the treatment of cancer and infectious diseases. © 2012 Fávaro et al.; licensee BioMed Central Ltd.
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Rights: aberto
Identifier DOI: 10.1186/1750-9378-7-14
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-84862259318&partnerID=40&md5=26a73c3bcf4343ac2d40f980e2e2ddba
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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