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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effects of melatonin on HIF-1 alpha and VEGF expression and on the invasive properties of hepatocarcinoma cells

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Colombo, Jucimara ; Wolf Maciel, Joao Marcos ; Ferreira, Livia Carvalho ; Da Silva, Renato Ferreira ; Pires De Campos Zuccari, Debora Aparecida
Total Authors: 5
Document type: Journal article
Source: Oncology Letters; v. 12, n. 1, p. 231-237, JUL 2016.
Web of Science Citations: 19

Liver cancer is the sixth most commonly occurring cancer globally, and the main histological type is hepatocellular carcinoma. This type of neoplasia has a poor prognosis due to a high rate of recurrence and intrahepatic metastasis, which are closely are closely associated with the angiogenic process. Vascular endothelial growth factor (VE6E), which is under the control of hypoxia inducible factor-1 alpha (HIF-1 alpha), stimulates the proliferation of endothelial cells and increases cell permeability, promoting the growth, spread and metastasis of tumors. Melatonin, the niain hormone secreted by the pineal gland, may have a significant role in tumor suppression and has demonstrated antiangiogenic and antimetastatic effects. The aim of the present study was to analyze the cell viability-, migration and invasion, as well as the expression of proangiogenic proteins VEGF and HIF-1 alpha, in HepG2 hepatocarcinoma cells, following treatment with melatonin. Cells were cultured and cell viability was investigated using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MIT) assay. The expression of proangiogenic proteins VEGF and HIF-1 alpha, under conditions of normoxia and hypoxia, was verified using immunocytochemistry and quantified by densitometry. The analysis of the processes of cell migration and invasion was performed in a Boyden chamber. The MIT assay revealed a reduction in cell viability (P=0.018) following treatment with ntM melatonin for 24 h. The expression of proangiogenic proteins VEGF and HIF-1 alpha was reduced in cells treated with miNt melatonin for 24 h in normoxic (P<0.001) and hypoxic (P<0.001) conditions, compared with the control group and with induced hypoxia alone. The rate of cell migration and invasion VMS additionally reduced in cells treated with 1 mkt melatonin for 48 h when compared with the control group (P=0.496). The results of the present study suggest that melatonin may have an antiproliferative, antiangiogenic and antimetastatic role in hepatocarcinoma cells and may present a novel therapeutic option for the treatment of liver cancer. (AU)

FAPESP's process: 13/06421-8 - Immunocytochemistry analysis of angiogenesis and apoptosis in hepatocellular Carcinoma cell line in response to treatment with melatonin
Grantee:João Marcos Wolf Maciel
Support Opportunities: Scholarships in Brazil - Scientific Initiation