Melatonin Differentially Modulates NF-кB Expression in Breast and Liver Cancer Cells

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,Brazil

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.

Cite this article as:

Colombo Jucimara, Jardim-Perassi V. Bruna , Ferreira P.S. João, Braga Z. Cristine , Sonehara M. Nathália, Júnior P. Rubens , Moschetta G. Marina , Girol P. Ana and Zuccari A.P.C. Debora *, Melatonin Differentially Modulates NF-кB Expression in Breast and Liver Cancer Cells, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (12) . https://dx.doi.org/10.2174/1871520618666180131112304