Affiliation:
1. Laboratorio de Investigacao Molecular no Cancer (LIMC), Faculdade de Medicina de Sao Jose do Rio Preto/FAMERP, Av. Brigadeiro Faria Lima, 5416, 15090-000 – Sao Jose do Rio Preto, SP, Brazil
2. Integrated College Padre Albino Foundation (FIPA), Catanduva, Sao Paulo, Brazil
Abstract
Background:
NF-kB (nuclear factor kappa B) is a transcription factor composed of two subunits, p50
and p65, which plays a key role in the inflammatory process. Melatonin has oncostatic, antiangiogenic and
antimetastatic properties, and some recent studies have indicated an inhibitory effect of melatonin on NF-kB in
some types of cancer. This work aims to investigate the effects of melatonin treatment on the expression of NFkB
in breast and liver cancer models.
Method:
The breast cancer xenographic model was performed using female Balb/c nude athymic mice injected
with MDA-MB-231 cells. The animals were treated with 40 mg/Kg of melatonin for 21 days. Volume of the
tumors was measured with a digital caliper. Hepatocarcinoma model was developed by using the HepG2 cells in
vitro, treated with 1 mM melatonin for 24 h. The expression of NF-kB protein was verified by immunohistochemistry
and immunocytochemistry and quantified by optical densitometry, in vivo study and in vitro study,
respectively. NF-kB gene expression was performed by quantitative RT-PCR.
Results:
The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size (P=0.0022).
There was a decrease in NF-kB protein staining (P=0.0027) and gene expression (P=0.0185) in mice treated
with melatonin. The opposite results were observed for the hepatocarcinoma model. HepG2 cells treated with
melatonin showed an increase in the NF-kB immunostaining when compared to control cells (P=0.0042).
Conclusion:
Our results indicated that the treatment with melatonin was able to decrease both gene and protein
expressions of NF-kB in breast cancer cells and, conversely, increase the transcription factor protein expression
in hepatocarcinoma cells. These data highlighted a double role in the expression of NF-kB, depending on the
cell type. Further studies are needed to better elucidate the action of melatonin in NF-kB, since this transcription
factor acts on different signaling pathways that are fundamental for carcinogenesis.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
27 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献