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RETRACTED: Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells
Author(s) -
CarbajoPescador Sara,
MartínRenedo Javier,
GarcíaPalomo Andrés,
Tuñón María J.,
Mauriz José L.,
GonzálezGallego Javier
Publication year - 2009
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2009.00719.x
Subject(s) - melatonin , melatonin receptor , receptor , endocrinology , medicine , biology , cell cycle , cell growth , apoptosis , nuclear receptor , biochemistry , transcription factor , gene
Hepatocellular carcinoma (HCC) is one of the most common cancers and its incidence is increasing worldwide. Melatonin, an indoleamine hormone, exerts anti‐oxidant, immunomodulatory, anti‐aging, and antitumor effects. Previous studies have shown that melatonin can act through specific receptors, including MT 1 , MT 2 , MT 3 receptors as well as a nuclear receptor belonging to the orphan nuclear receptor family. Recently, we have described their role in the oncostatic and pro‐apoptotic effects of melatonin on HepG2 human HCC cells. However, the potential role of the different melatonin cellular receptors on its antiproliferative effects remains unknown. In the present study, we examined the effect of melatonin treatment on HepG2 human HCC cells, analyzing cell cycle arrest and melatonin receptor expression. Melatonin was administered for 2, 4, and 6 days at 1000 or 2500 μ m . Melatonin induced a dose‐ and time‐dependent inhibition on cell proliferation. This treatment caused an alteration in the cell cycle, with an increase in the number of cells in G 2 /M phase at both 1000 and 2500 μ m melatonin concentrations, and a significant increase on S phase cell percentage by the highest dose. Furthermore, increases in protein expression of MT 1 , MT 3 , and retinoic acid‐related orphan receptor‐α were found after melatonin treatments. These increases were coincident with a significant induction in the expression of p21 protein, which negatively regulates cell cycle progression. Our results confirm the antitumor effect of melatonin in HCC cells, suggesting that its oncostatic properties are related, at least in part, to changes on the expression of their different subtypes of receptors.