Title:Melatonin Differentially Modulates NF-кB Expression in Breast and Liver Cancer Cells
VOLUME: 18 ISSUE: 12
Author(s):Jucimara Colombo, Bruna V. Jardim-Perassi, João P.S. Ferreira, Cristine Z. Braga, Nathália M. Sonehara, Rubens P. Júnior, Marina G. Moschetta, Ana P. Girol and Debora A.P.C. Zuccari*
Affiliation: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, 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, 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, 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, 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, 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, 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, Integrated College Padre Albino Foundation (FIPA), Catanduva, Sao Paulo, 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
Keywords:NF-kB, breast cancer, hepatocellular carcinoma, melatonin, liver cancer, HepG2 cells.
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.
