P-mapa, a promisor immunomodulator against tumor cells of colonic tissues: An investigation of the action mechanism over the TLR4 signaling pathway.

Abstract

Colorectal cancer (CRC) is a multifactorial syndrome that drives to uncontrollable cell division, genetic alterations, and functional alteration. In the present work, we evaluated the immunomodulatory properties of P-mapa, a compound extracted from Aspergillus oryzae fungus, versus Fluorouracil (5-FU) treatment in chemically induced CRC. CRC was induced by DMH in F344 rats. Animals of treated groups receive weekly 15 mg/Kg of 5-FU or 5 mg/Kg of P-mapa, over 10 weeks. Tissues were stained for aberrant crypt foci (ACF) counting and histopathology evaluation, immunostained for TLR4 pathways and quantified for TNFα Cytokine assay. DMH was efficient to induce hyperplastic lesions and ACF. Both treatments reduced significantly ACF formation and tumor aggressiveness. Immunohistochemistry for TLR4 signaling reveals that both treatments had no effect over the TLR4-NFκB signaling pathway. On the other hand, both succeed in increase interferon signaling, with activation of the TRIF-IRF3 pathway and consequently inducing IFNγ synthesis. The present results show the immunomodulatory properties of P-mapa in chemically induced CRC model. P-mapa induced a significant increase in Type-I IFNs synthesis and subsequently immune cell recruitment, resulting in an increase of IFNγ concentration in colorectal mucosa and its inhibitory effects over tumoral growth. In this scenario, P-mapa showed an interesting antitumoral effect by inhibiting tumor growth.

• Authors: Eduardo Augusto Rabelo Socca, Sabrina Karen Reis, Sandra Cristina Genaro, Stephanie Kussik Leite, Ianny Brum Reis, Petra Karla Bockëlmann, Nelson Durán, Wagner José Fávaro
• Journal: Life sciences (Life Sci) Vol. 242 Pg. 117185 (Feb 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31862453 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biopolymers
• Immunologic Factors
• Linoleic Acids
• Oleic Acids
• P-mapa
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Fluorouracil

Topics

• Aberrant Crypt Foci (pathology)
• Animals
• Antineoplastic Agents (therapeutic use)
• Biopolymers (therapeutic use)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Fluorouracil (therapeutic use)
• Immunologic Factors (therapeutic use)
• Linoleic Acids (therapeutic use)
• Male
• Oleic Acids (therapeutic use)
• Rats
• Rats, Inbred F344
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)