Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells
Article first published online: 10 OCT 2009
© 2009 The Authors. Journal compilation © 2009 John Wiley & Sons A/S
Journal of Pineal Research
Volume 47, Issue 4, pages 330–338, November 2009
How to Cite
Carbajo-Pescador, S., Martín-Renedo, J., García-Palomo, A., Tuñón, M. J., Mauriz, J. L. and González-Gallego, J. (2009), Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells. Journal of Pineal Research, 47: 330–338. doi: 10.1111/j.1600-079X.2009.00719.x
- Issue published online: 14 OCT 2009
- Article first published online: 10 OCT 2009
- Received July 23, 2009; accepted September 11, 2009.
- cell cycle;
Abstract: 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 MT1, MT2, MT3 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 μm. 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 G2/M phase at both 1000 and 2500 μm melatonin concentrations, and a significant increase on S phase cell percentage by the highest dose. Furthermore, increases in protein expression of MT1, MT3, 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.