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

Author(s)

Colombo, Jucimara ^{[1, 2, 3]} ; Jardim-Perassi, V, Bruna ; Ferreira, Joao P. S. ^{[4, 5, 6, 7]} ; Braga, Cristine Z. ^{[4, 5, 6, 7]} ; Sonehara, Nathalia M. ^{[4, 6, 7, 8]} ; Rubens, P. Junior ^{[4, 6, 7, 8]} ; Moschetta, Marina G. ^{[4, 6, 7]} ; Girol, Ma P. ^{[9, 10]} ; Zuccari, Debora A. P. C. ^{[4, 6]}

Affiliation

^[1] FAMERP, Dept Mol Biol, Sao Jose Do Rio Preto, SP - Brazil

^[2] UNESP IBILCE, Program Postgrad Genet, Sao Jose Do Rio Preto, SP - Brazil

^[3] Fac Med Sao Jose do Rio Preto FAMERP, LIMC, Av Brigadeiro Faria Lima 5416, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[4] Jardim-Perassi, Bruna, V, Fac Med Sao Jose do Rio Preto FAMERP, LIMC, Av Brigadeiro Faria Lima 5416, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[5] FAMERP, Dept Mol Biol, Fac Med Sao Jose do Rio Preto, BR-15090000 Sao Paulo, SP - Brazil

^[6] Jardim-Perassi, Bruna, V, FAMERP, Dept Mol Biol, Sao Jose Do Rio Preto, SP - Brazil

^[7] Jardim-Perassi, Bruna, V, UNESP IBILCE, Program Postgrad Genet, Sao Jose Do Rio Preto, SP - Brazil

^[8] FAMERP, PostGrad Program Hlth Sci, Fac Med Sao Jose do Rio Preto, Av Brigadeiro Faria Lima 5416, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[9] Integrated Coll Padre Albino Fdn FIPA, Catanduva, SP - Brazil

^[10] Sao Paulo State Univ UNESP, Lab Immunomorphol, Dept Biol, Sao Jose Do Rio Preto - Brazil

• Document type: Journal article
• Source: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 18, n. 12, p. 1688-1694, 2018.
• Web of Science Citations: 3

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 NF-kB 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. Hepatocarcinonia 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. (AU)

• FAPESP's process: 14/25661-2 - NF-kB and VEGF expression in animal model of breast cancer after melatonin treatment
• Grantee: João Paulo Senna Ferreira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation