Author(s):
Chuffa, Luiz Gustavo de Almeida [UNESP] ; Fioruci-Fontanelli, Beatriz Aparecida [UNESP] ; Mendes, Leonardo de Oliveira [UNESP] ; Seiva, Fábio Rodrigues Ferreira ; Martinez, Marcelo ; Favaro, Wagner José ; Domeniconi, Raquel Fantin [UNESP] ; Pinheiro, Patricia Fernanda Felipe [UNESP] ; Santos, Lucilene Delazari dos [UNESP] ; Martinez, Francisco Eduardo
Date: 2015
Persistent ID: http://hdl.handle.net/11449/128549
Origin: Oasisbr
Subject(s): Ovarian cancer; Melatonin; Inflammation; TLR4; MyD88; TRIF
Description
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Background: Toll-like receptors (TLRs) are effector molecules expressed on the surface of ovarian cancer (OC) cells, but the functions of the TLR2/TLR4 signaling pathways in these cells remain unclear. Melatonin (mel) acts as an anti-inflammatory factor and has been reported to modulate TLRs in some aggressive tumor cell types. Therefore, we investigated OC and the effect of long-term mel therapy on the signaling pathways mediated by TLR2 and TLR4 via myeloid differentiation factor 88 (MyD88) and toll-like receptor-associated activator of interferon (TRIF) in an ethanol-preferring rat model.Methods: To induce OC, the left ovary of animals either consuming 10% (v/v) ethanol or not was injected directly under the bursa with a single dose of 100 mu g of 7,12-dimethylbenz(a) anthracene (DMBA) dissolved in 10 mu L of sesame oil. The right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of mel (200 mu g/100 g b.w./day) for 60 days.Results: Although mel therapy was unable to reduce TLR2 levels, it was able to suppress the OC-associated increase in the levels of the following proteins: TLR4, MyD88, nuclear factor kappa B (NFkB p65), inhibitor of NFkB alpha (IkB alpha), IkB kinase alpha (IKK-alpha), TNF receptor-associated factor 6 (TRAF6), TRIF, interferon regulatory factor 3 (IRF3), interferon beta (IFN-beta), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6. In addition, mel significantly attenuated the expression of IkB alpha, NFkB p65, TRIF and IRF-3, which are involved in TLR4-mediated signaling in OC during ethanol intake.Conclusion: Collectively, our results suggest that mel attenuates the TLR4-induced MyD88- and TRIF-dependent signaling pathways in ethanol-preferring rats with OC.
Universidade Estadual do Norte do Paraná, Instituto de Biologia, Campus Luiz Meneghel
Universidade Federal de São Carlos, Departamento de Morfologia e Patologia
Universidade Estadual de Campinas, Departamento de Anatomia, Biologia Celular e Fisiologia e Biofísica, Instituto de Biologia
Universidade Estadual Paulista, Departamento de Anatomia, Instituto de Biociências de Botucatu
Universidade Estadual Paulista, Centro de Venenos e Animais Peçonhentos de Botucatu
FAPESP: 2011/19294-9
FAPESP: 2013/02466-7
