Abstract
Context:
Chemotherapy is a cornerstone in the treatment of hepatocellular carcinoma (HCC). Melatonin is a pineal hormone that targets various cancers, however, its antitumor pathways are still not fully elucidated.
Objective:
This study investigated melatonin's antitumor molecular mechanisms to inhibit the proliferation of HepG2 cells.
Materials and methods:
HepG2 Cells were classified into cells without treatment as a control group and cells treated with melatonin (5.4 mmol/L) for 48 h. Proliferating cell nuclear antigen (PCNA) and marker of proliferation Ki-67 were estimated using immunohistochemical analysis. Apoptosis and cell cycle were evaluated using flow cytometric analysis. Apoptotic markers were detected using RT-qPCR assay. Antioxidants and oxidative stress biomarkers were performed using a colorimetric assay.
Results:
Melatonin produced a remarkable steady decrease in the viability of HepG2 cells at a concentration range between 5-20 mmol/L. Melatonin suppressed cell proliferation in the G2/M phase of the cell cycle (34.97 ± 0.92%) and induced apoptosis (12.43 ± 0.73%) through up-regulating p21 and p53 that was confirmed by the reduction of PCNA and Ki-67 expressions. Additionally, melatonin repressed angiogenesis evidenced by the down-regulation of angiopoietin-2, vascular endothelial growth factor receptor-2 expressions (0.42-fold change), and the level of CD133. Moreover, melatonin augmented the oxidative stress manifested by a marked increase of 4-hydroxynonenal levels with a reduction of glutathione content and superoxide dismutase activity.
Discussion and conclusion:
Melatonin inhibits proliferation and angiogenesis and induced apoptosis and oxidative stress in HepG2 cells. These results indicate the oncostatic effectiveness of melatonin on liver cancer.
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