However, its consumption should be cautious to avoid the development of drug resistance and provide a better treatment strategy. Collectively, melatonin is an effective anti-inflammatory and anti-proliferative promising therapy for the treatment of HCC. This action is initiated through cell cycle arrest at G0/G1 phase via increasing the expression of P53, but independently on apoptosis. Accordingly, we can conclude that melatonin facilitates the anti-proliferation of cells at doses of 1 mM, and 2.5 mM after 24 h. Our study proved the anti-inflammatory activity of 1 mM melatonin in HCC-HepG2 cells. Interestingly, we detected observed increases in the expression levels of genes responsible for conferring drug resistance including ABCB1, ABCC1, and ABCC5. On contrary, as a novelty, our data recorded decreases in expression levels of genes involved in the pro-apoptotic pathway with a significant increase ( P < 0.05) in the expression level of an anti-apoptotic gene, Bcl2.
Our results validated that, melatonin shows anti-proliferative action through preserving cells in G0/G1 phase ( P < 0.001) that is associated with a highly significant increase in the expression level of the P53 gene ( P < 0.01). Additionally, the Human inflammation antibody array membrane (40 targets) was used to check the anti-inflammatory effect of melatonin.
Furthermore, the molecular patterns of genes that contributed to apoptosis, drug resistance development, antioxidation, and melatonin crossing were quantified by qRT-PCR. The selected minimal proliferation inhibition doses of melatonin were then incubated with cells to examine the arresting effect of melatonin on dividing cells using flow cytometry. To achieve the aim of the present study, HCC-HepG2 cells were treated with different concentrations of melatonin at various time intervals. Although, melatonin has various antitumor bioactivities there is a requirement for more investigations to elucidate the not discussed effects, and the controversial responses of the treatment with melatonin on targets mediated in HCC. Hepatocellular carcinoma (HCC) is the major lethal primary liver malignant worldwide.
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