Abstract
ContextChemotherapy 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. ObjectiveThis study investigated melatonin's antitumor molecular mechanisms to inhibit the proliferation of HepG2 cells. Materials and methodsHepG2 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. ResultsMelatonin 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 conclusionMelatonin inhibits proliferation and angiogenesis and induced apoptosis and oxidative stress in HepG2 cells. These results indicate the oncostatic effectiveness of melatonin on liver cancer.
Highlights
Hepatocellular carcinoma (HCC) is life-threatening cancer and deserves considerable research for finding successful chemotherapy (Yang et al, 2019)
The percentages of Proliferating cell nuclear antigen (PCNA) and Ki-67 expression were significantly decreased (P < 0.001) by 24.7 Æ 1.07% and 39.4 Æ 1.7% respectively after treatment with melatonin. These findings indicate that melatonin caused a significant decrease in the proliferation of HepG2 cells
The cell population in G2/M was significantly (P < 0.001) higher in melatonin-treated cells than untreated cells. These findings indicate cell cycle arrest of HepG2 cells treated with melatonin at the G2/M phase
Summary
Hepatocellular carcinoma (HCC) is life-threatening cancer and deserves considerable research for finding successful chemotherapy (Yang et al, 2019). Chemotherapy either alone or with other modalities is the main intervention option for HCC. The cytotoxicity and harmful side effects of drugs used for HCC are limiting factors in chemotherapy of patients. Searching for effective and safe antitumor drugs is an essential issue. It is reported that HCC cells can resist conventional chemotherapeutic drugs (Jin et al, 2015). The main mechanism of cancer growth and progression is avoiding apoptosis and accelerating cell division (Lin et al, 2017). Selective apoptosis inductors and cell cycle suppressors have emerged as a promising strategy for developing a specific drug for cancer treatment (Mortezaee et al, 2019). Angiogenesis is an important process for cancer growth and progression and blocking this process is an effective approach in the treatment of cancers
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have